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Biomedical subjects

A J Hance

Publications and source records attributed to A J Hance.

At least 55 records · Page 3Linked to original sources

Evaluation of clinical judgment in the identification and treatment of nosocomial pneumonia in ventilated patients.

To evaluate the accuracy of clinical judgment in the diagnosis and treatment of nosocomial pneumonia in ventilated patients, we studied 84 patients suspected of having nosocomial pneumonia because of the presence of a new pulmonary infiltrate and purulent tracheal secretions. We prospectively evaluated the accuracy of diagnostic predictions and therapeutic plans independently formulated by a team of physicians aware of all clinical, radiologic and laboratory data, including the results of Gram-stained bronchial aspirates. Definite (n = 51) or probable (n = 33) diagnoses could be established in all patients by strict histopathologic and/or bacteriologic criteria. Only 27/84 patients were diagnosed as having pneumonia. Organisms responsible for pneumonias were identified by quantitative cultures of samples obtained using a protected specimen brush or pleural fluid cultures. Four hundred eight predictions were made for the 84 studied patients. Clinical diagnoses for patients subsequently diagnosed as having pneumonia were accurate in 81/131 cases (62 percent). Furthermore, only 43/131 (33 percent) therapeutic plans proposed for these patients represented effective therapy. Common causes of inappropriate treatment included failure to diagnose pneumonia (50 plans), failure to effectively treat highly resistant organisms (21 plans), and failure to treat all organisms in cases of polymicrobial pneumonia (14 plans). Therapeutic plans formulated for patients without pneumonia included the unnecessary use of antibiotics in 45/277 cases (16 percent). These findings indicate that the use of clinical criteria alone does not permit the accurate diagnosis of nosocomial pneumonia in ventilated patients, and commonly results in inappropriate or inadequate antibiotic therapy for these patients.

Bacterial Infections↗

Pulmonary immune cells in health and disease: dendritic cells and Langerhans' cells.

The activation of T-lymphocytes recognizing specific antigens is a crucial and early event in the development of an immune response, but T-lymphocytes cannot respond to antigens without help of a second cell type called accessory cells or antigen-presenting cells. Studies from several groups have indicated that pulmonary dendritic cells and Langerhans' cells, like their counterparts in other tissues, are potent accessory cells, and suggest that these cells may play an extremely important role in initiating lung immune responses. The purpose of this review is to summarize current information concerning pulmonary dendritic cells and Langerhans' cells, including their origin, distribution in the lung and functional capabilities. The possible role of these cells in certain lung diseases of immune origin will also be discussed.

Animals↗

Restricted diversity of V gamma 9-JP rearrangements in unstimulated human gamma/delta T lymphocytes.

The diversity of human peripheral blood gamma/delta T cells is known to be limited by the preferential use of V genes coding for V gamma 9 (usually linked to JP) and V delta 2. We show that the diversity of these cells is further limited at the junctional region. First, an identical rearrangement is found in 10%-30% of all gamma/delta T cells which contain V gamma 9-JP rearrangements. Second, the vast majority of V gamma 9-JP rearrangements which are different from this predominant sequence have, nevertheless, the same length or code for variable regions whose length differs by only one amino acid (+/- 1). Overall, 30%-50% of V gamma 9-JP rearrangements have a junctional region which encodes for a peptide with the amino acid sequence E VX EL, in which EV is predominantly, but not exclusively, encoded by the germ-line V gamma 9 sequence and EL is encoded by JP. The X amino acid is variable, but a glutamine is over-represented. The diversity of the V gamma 9-JP repertoire is fairly constant in different individuals and at different ages, including before, during and after the post-natal expansion of peripheral blood gamma/delta T cells.

Adult↗

Lymphocytes infiltrating normal human lung and lung carcinomas rarely express gamma delta T cell antigen receptors.

It has been suggested that T lymphocytes expressing gamma delta T cell receptors (TCR) could play an important role in the defence of epithelia against infection and neoplastic transformation, but the potential for gamma delta T lymphocytes to serve these functions in human respiratory epithelium has received little attention. In this study, we used immunohistochemical techniques and specific monoclonal antibodies to characterize the number and distribution of T lymphocytes expressing alpha beta and gamma delta TCR in normal human lung and in lung carcinomas. T lymphocytes present in normal bronchi and alveolar parenchyma were predominantly of the alpha beta TCR phenotype, whereas gamma delta T lymphocytes represented only 1.1 +/- 0.7% and 1.3 +/- 0.5% of total CD3+ lymphocytes respectively. An important lymphocytic infiltration was noted in the stroma of all primary lung carcinomas examined, and some T lymphocytes were also present infiltrating between tumour cells. These T lymphocytes were almost entirely alpha beta T cells and only rare gamma delta T cells were found, regardless of the histologic type of carcinoma (0.8 +/- 0.1% of CD3+ T cells). This study demonstrates that T cells present in normal bronchi and lung parenchyma and those infiltrating primary lung carcinomas express predominantly alpha beta TCR. These findings do not support the conclusion that gamma delta T lymphocytes play an important role either in the defence of human lung epithelia or in immune responses directed against primary lung carcinomas.

Adenocarcinoma↗

Detection of mycobacterial DNA in pleural fluid from patients with tuberculous pleurisy by means of the polymerase chain reaction: comparison of two protocols.

BACKGROUND: The detection of mycobacterial DNA in clinical samples on the basis of the polymerase chain reaction is a promising approach for the rapid diagnosis of tuberculous infections. No consensus exists, however, about which protocols are most sensitive, and the usefulness of this approach in the diagnosis of tuberculous effusions has been assessed in few patients. METHODS: The sensitivity of two protocols was compared for the detection of DNA from Mycobacterium tuberculosis in samples containing known amounts of mycobacterial DNA and in DNA extracted from 15 tuberculous pleural effusions. The results obtained for pleural fluid have been compared with cytological findings and with results obtained by standard microbiological techniques. RESULTS: Mycobacteria could be detected by acid fast staining in none and by culture in three of the 15 pleural fluid samples. A protocol based on the detection of the IS6110 insertion element (which could detect one mycobacterial genome/sample reproducibly) gave a positive result in nine of the 15 tuberculous effusions, though some samples were only intermittently positive (p less than 0.05 compared with culture). In contrast, a protocol based on the detection of the gene coding for the 65 kD mycobacterial antigen (which could detect mycobacterial genomes only if there were at least 10/sample) gave a positive result in three of the 15 tuberculous effusions. Pleural fluid that was always positive with the amplification procedure detecting the IS6110 sequence contained more neutrophils (30% (SD 27%)) than samples that were intermittently positive or always negative (3% (3%)); mycobacterial DNA was never detected in the four samples containing less than 1% neutrophils. CONCLUSIONS: The amplification of the IS6110 insertion element represents a rapid and sensitive means of detecting M tuberculosis in tuberculous effusions. The enrichment of cells containing mycobacteria (possibly neutrophils) before DNA extraction may be required to improve the sensitivity of this approach.

DNA Transposable Elements↗

Pulmonary Langerhans' cell granulomatosis (histiocytosis X).

Pulmonary Langerhans' cell granulomatosis is usually classified among the lung diseases of unknown origin. Better appreciation of the characteristic clinical features of this disease, more detailed description of the pathologic lesions, and recent advances in the basic biology of Langerhans' cells have provided new insights into the pathogenesis of this process.

Cell Transformation, Neoplastic↗

A search for mycobacterial DNA in granulomatous tissues from patients with sarcoidosis using the polymerase chain reaction.

We have used the polymerase chain reaction as a tool to detect the presence of mycobacterial DNA from organisms of the Mycobacterium tuberculosis complex and other species of mycobacteria in samples from patients with sarcoidosis. Using systems based on the amplification of a fragment of the gene coding for the 65-kD mycobacterial antigen, which were demonstrated to detect approximately 20 mycobacterial genomes/microgram total DNA, DNA from M. tuberculosis was reproducibly identified in DNA extracted from granulomatous tissues from two patients with sarcoidosis, but could not be detected in DNA extracted from tissue biopsies (n = 16) or cells recovered by lavage (n = 6) from most sarcoid patients or from control subjects (n = 22). Using a system based on the amplification of a fragment of the IS6110 insertion element, which could reliably detect two genomes of mycobacterial DNA/microgram total DNA, no additional positive results were observed. In an effort to identify another species of Mycobacterium present in granulomatous tissues from sarcoid patients but not control tissues, a fragment of the 65-kD mycobacterial antigen was amplified and then reamplified using "nested" primers recognizing sequences that are highly conserved among mycobacteria and closely related species, and the amplified DNA products were cloned and sequenced. Amplified DNA was observed in a minority of samples from patients and control subjects (32/84 and 34/77 attempts, respectively, p greater than 0.2), resulting from amplification of DNA from at least 17 different organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Characterization of gamma/delta T-lymphocytes in the peripheral blood of patients with active tuberculosis. A comparison with normal subjects and patients with sarcoidosis.

Studies in experimental animals have suggested that gamma/delta T-cells play an important role in the immune response against mycobacteria, but evidence for the participation of these cells in the course of human tuberculosis remains fragmentary. We have evaluated the number and state of activation of gamma/delta T-cells in the peripheral blood of patients with active tuberculosis using two-color cytofluorometry, and we have sought evidence that these cells might play a role in the impaired responses to recall antigens seen in some patients by comparing the proliferation of blood T-lymphocytes before and after removing gamma/delta T-cells by panning. Results were compared with those obtained for cells from normal subjects and from patients with sarcoidosis. The proportion and absolute number of circulating CD3+ gamma/delta T-cells were not significantly different comparing blood from patients with tuberculosis and that from control subjects [54.6 +/- 39.9 (n = 17) and 59.1 +/- 30.2 cells/microliters (n = 10), respectively, p > 0.2], and the proportion of cells expressing receptors using the V delta 1 variable region remained unchanged in patients with tuberculosis. Few gamma/delta T-cells from patients with tuberculosis expressed surface antigens associated with activation (IL-2R, < 1%; HLA-DR, 2.6 +/- 3.4%). Four of 15 patients with sarcoidosis had a proportion of gamma/delta T-cells that was outside the range observed in normal subjects, but the absolute number of CD3+ gamma/delta T-lymphocytes was not different comparing the two groups (p > 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Use of a reamplification protocol improves sensitivity of detection of Mycobacterium tuberculosis in clinical samples by amplification of DNA.

We have compared the sensitivity and specificity of quantitative mycobacterial culture against results obtained by using the polymerase chain reaction for the detection of DNA from organisms of the Mycobacterium tuberculosis complex in 82 clinical specimens from patients suspected of having tuberculosis. Two amplification protocols were used, a standard amplification protocol, which amplifies a segment of the gene coding for the 65-kDa antigen, and a protocol in which the initial amplification products are reamplified with a second set of nested oligonucleotide primers. Although the standard amplification protocol gave positive results for 18 of 18 samples which grew greater than 100 CFU/ml and gave positive results in 4 of 35 specimens from patients with tuberculosis which were negative by culture, only 1 of 6 samples which grew less than 100 CFU/ml was positive. This lack of sensitivity could not be explained by the presence of inhibitors of Taq polymerase present in the original samples. In contrast, the reamplification protocol gave positive results for 24 of 24 samples which were positive by culture as well as for 13 of 35 samples from patients with tuberculosis which were negative by culture (overall sensitivity, 63%, P less than 0.02, compared with the standard amplification protocol and routine culture). Two of 23 samples from patients not diagnosed as having tuberculosis gave positive results when the standard amplification protocol was used, but no additional false-positive results were seen with the reamplification protocol (overall specificity, 91%). We conclude that the use of a reamplification protocol improves the sensitivity of detection of mycobacterial DNA in clinical samples without sacrificing specificity. The sensitivity of this approach appears to be superior to that of standard culture techniques.

Base Sequence↗

Expression of 1,25(OH)2D3 receptors on alveolar lymphocytes from patients with pulmonary granulomatous diseases.

1,25(OH)2D3 is known to be produced at sites of granulomatous reactions. In order to characterize the cell types that are targets for this immunoregulatory hormone, we have evaluated the expression of 1,25(OH)2D3 receptors on peripheral blood T-lymphocytes and those recovered from the lung by bronchoalveolar lavage from patients with pulmonary granulomatous diseases (tuberculosis and sarcoidosis) and from normal control subjects using combined autoradiographic and immunohistochemical techniques. Lavage T-lymphocytes from patients with tuberculosis or with sarcoidosis, but not those from normal control subjects, expressed 1,25(OH)2D3 receptors as demonstrated by binding of [3H]1,25(OH)2D3, which was inhibited by the presence of excess unlabeled 1,25(OH)2D3, but not by the presence of unlabeled 25(OH)D3 (receptor-positive lymphocytes: sarcoidosis, 20 +/- 12%; tuberculosis, 31 +/- 17%). In contrast, blood lymphocytes from patients with granulomatous diseases did not express detectable 1,25(OH)2D3 receptors. The percentage of lavage T-lymphocytes expressing 1,25(OH)2D3 receptors was significantly greater for patients with tuberculosis presenting with isolated hilar adenopathy than for patients with pulmonary infiltrates and/or cavities. 1,25(OH)2D3 receptors were expressed to a greater extent on CD8+ T-lymphocytes than on CD4+ T-lymphocytes in sarcoidosis, whereas a greater proportion of CD4+ than of CD8+ T-lymphocytes from patients with tuberculosis were receptor-positive. These findings support the conclusion that the interaction of 1,25(OH)2D3 with its receptor on T-lymphocytes may play an important role in the regulation of granulomatous reactions, but because these receptors are expressed on different lymphocyte populations, the net effect of this potent immunoregulatory molecule is likely different in sarcoidosis and tuberculosis.

Adult↗

Bronchoalveolar mast cells in normal farmers and subjects with farmer's lung. Diagnostic, prognostic, and physiologic significance.

To evaluate the specificity and significance of increased lavage mast cells in farmer's lung, we examined the lavage cell differentials of 89 farmers and 19 normal nonfarming control subjects. The farmers were divided into four groups: acute farmer's lung (n = 17), farmers with one or more prior episodes of farmer's lung who remained in daily contact with hay (n = 26) or quit farming (n = 14), and normal farmers (n = 36). A total of 14 of the subjects with prior episodes of farmer's lung and still farming and 15 normal farmers were evaluated twice at a 2-yr interval. The lavage mast cell numbers were significantly higher in acute farmer's lung (7.5 +/- 7.3 x 10(3)/ml, mean +/- SD) and ex-farmer's lung who were still farming (1.2 +/- 1.3 x 10(3)/ml) than in normal farmers (0.1 +/- 0.1 x 10(3)/ml) (p less than 0.01). A total of 8 of 14 exfarmer's lung patients who had quit farming and 18 of 36 normal farmers had an increased number of mast cells in lavage, but mast cell count never exceeded 0.5% of total recovered cells. In the acute farmer's lung and ex-farmer's lung-still farming groups, the mast cell count correlated with the lymphocyte count: r = 0.83 and r = 0.69 (p less than 0.001), respectively. In the two groups evaluated twice, mast cell numbers at the first study did not correlate with changes seen at the second study in chest roentgenogram and pulmonary functions. We conclude that an increase in lavage mast cells occurs commonly as a part of the immune response against thermophilic bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Antigen-induced proliferative response of lavage and blood T lymphocytes. Comparison of cells from normal subjects and patients with sarcoidosis.

To evaluate the mechanisms responsible for anergy in sarcoid patients, we studied the ability of highly purified lavage and blood T lymphocytes from control subjects and patients with sarcoidosis to proliferate in response to recall antigens, and compared the results of antigen-induced lymphocyte proliferation with the clinical characteristics of the patients. Both blood and lavage T lymphocytes from all control subjects proliferated in response to purified protein derivative (PPD) and candida antigens, and no significant difference was observed comparing the proliferation of lymphocytes from the two sources. The antigen-induced proliferation of blood and lavage T lymphocytes from sarcoid patients was reduced compared with that of the corresponding cell populations from normal subjects (p less than 0.01 for PPD, Candida, and tetanus), and the proliferative response of sarcoid lavage lymphocytes was significantly lower than that of blood T lymphocytes from these patients. No evidence for inhibition of T lymphocyte proliferation by accessory cells (blood monocytes) or CD8+ T lymphocytes was observed, and the refractory state could not be overcome by adding exogenous recombinant human IL-2 or IL-4. An inverse correlation was observed between the PPD-induced proliferation of sarcoid lavage T lymphocytes and criteria associated with "active" disease, including lymphocytes/ml lavage fluid (p less than 0.003), 67Ga uptake (p less than 0.005), and serum angiotensin converting enzyme activity (p less than 0.005). Lavage lymphocytes from patients studied early in the course of the disease proliferated better than those from patients with more long-standing disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Gamma/delta T-lymphocytes are not increased in number in granulomatous lesions of patients with tuberculosis or sarcoidosis.

gamma delta T-lymphocytes have been suggested to play a role in granuloma formation and to participate in the immune responses observed in tuberculosis and sarcoidosis. To further evaluate the role of gamma delta T-lymphocytes in these disorders, we used immunohistochemical techniques and specific monoclonal antibodies to characterize the number of distribution of T-lymphocytes expressing alpha beta and gamma delta T-cell receptors in granulomatous lesions from patients with sarcoidosis (n = 8) or tuberculosis (n = 4). The vast majority of T-lymphocytes present in lymph nodes from patients with tuberculosis or sarcoidosis expressed alpha beta TCR, whereas only rare gamma delta T-lymphocytes were observed inside or at the periphery of the granulomas. Recently formed granulomas induced by positive Kveim test reactions in patients with sarcoidosis also contained only small numbers of gamma delta T-lymphocytes, including those present in biopsies from two patients with increased numbers of circulating gamma delta T-lymphocytes. These observations demonstrate that T-cells involved in immune granulomatous reactions in sarcoidosis and tuberculosis express predominantly alpha beta TCR, and they do not support the conclusion that gamma delta T-lymphocytes necessarily play an important role in granuloma formation.

Adult↗

Spontaneous release of granulocyte colony-stimulating factor (G-CSF) by alveolar macrophages in the course of bacterial pneumonia and sarcoidosis: endotoxin-dependent and endotoxin-independent G-CSF release by cells recovered by bronchoalveolar lavage.

Because granulocyte colony-stimulating factor (G-CSF) is known to induce granulopoiesis and activate mature neutrophils, this factor could be important in determining the number and functional activity of neutrophils at sites of lung disease. The purpose of this study was to evaluate the ability of lung immune and inflammatory cells to produce G-CSF, and to seek evidence for the spontaneous production of this factor by cells recovered by lavage from controls and patients with lung diseases in which neutrophils may play a pathogenetic role. Lavage cells from controls produced little G-CSF spontaneously. Alveolar macrophages (AM), but not lymphocytes, produced large amounts following endotoxin stimulation. Lavage cells from patients with respiratory failure associated with bacterial pneumonia, but not those with respiratory failure from noninfectious causes, spontaneously released G-CSF (32 +/- 24 and less than 1 U/10(6) AM, respectively). Lavage cells from five of 15 patients with sarcoidosis and one of five patients with diffuse pulmonary fibrosis also spontaneously released G-CSF, which could not be explained by endotoxin exposure. The release of G-CSF by endotoxin-dependent and -independent mechanisms could play a role in the recruitment and activation of neutrophils in bacterial pneumonia and participate in the pathogenesis of some interstitial lung diseases.

Adult↗

[Pulmonary dendritic cells].

The dendritic cells were initially described in lymphoid organs and have been recently shown in the normal human lung at the level of the bronchioles, preferentially in the peribronchiolar connective tissue and in the alveolar parenchyma. Langerhans cells, which constitute a sub-population amongst the dendritic cells are equally present, but virtually exclusively limited to the bronchiolar epithelium. The pulmonary Langerhans cells probably derive from dendritic cells as in the skin. The number and state of differentiation of pulmonary dendritic cells vary as a function of the epithelial microenvironment which seems necessary in the differentiation of dendritic cells into Langerhans cells. Langerhans cells are frequently seen in zones of alveolar hyperplasia and/or alveolar metaplasia induced by tobacco or by inflammatory lesions. Dendritic cells and Langerhans cells have a potent capacity for presenting an antigen to lymphocytes. Their presence in the normal lung and their differentiation in the course of certain pathological pulmonary processes strongly suggest that they have a significant role in the pulmonary immune response as well as in the pathogenesis of certain diseases.

Dendritic Cells↗

Bronchoalveolar lavage for rapid diagnosis of the fat embolism syndrome in trauma patients.

OBJECTIVE: To evaluate the usefulness of bronchoalveolar lavage in establishing the diagnosis of the fat embolism syndrome in trauma patients with long-bone fractures. DESIGN: Case series. SETTING: Referral hospital. PATIENTS: Eighteen trauma patients with long-bone fractures, including 5 with definite fat embolism syndrome, 5 in whom the diagnosis had been clinically suspected but was impossible to confirm or exclude before bronchoscopy, and 8 with no clinical evidence of the syndrome. Control groups included 9 patients without previous trauma who developed the adult respiratory distress syndrome for various reasons and 15 normal volunteers. MEASUREMENTS AND MAIN RESULTS: Each patient had fiber-optic bronchoscopy with bronchoalveolar lavage, and the percentage of lavage cells containing intracellular fat droplets stained with oil red 0 were determined. In the five patients with definite fat embolism syndrome, light microscopic study of bronchoalveolar cells stained with oil red 0 showed many large intracellular fat droplets (mean percentage of cells containing fat droplets, 63%; range, 31% to 82%), whereas less than 2% of cells recovered by lavage from trauma patients with no clinical evidence of the syndrome, from patients with the adult respiratory distress syndrome, or from normal volunteers contained such inclusions. Use of the same technique in the five patients with possible fat embolism syndrome permitted the immediate identification of three patients in whom this diagnosis was later confirmed by subsequent autopsy or clinical follow-up. CONCLUSIONS: The identification of fat droplets within cells recovered by bronchoalveolar lavage in trauma patients may be a rapid and specific method for establishing the diagnosis of the fat embolism syndrome.

Adolescent↗

Expression of surface antigens distinguishing "naive" and previously activated lymphocytes in bronchoalveolar lavage fluid.

Studies in animals suggest that the initial activation of unprimed ("naive") T lymphocytes by inhaled antigens may occur outside the lung with later recruitment to the lung. If this is true all lymphocytes present in the lung should show evidence of prior activation. To test this hypothesis for lymphocytes present on the alveolar surface, the expression of surface antigens, which distinguish unprimed from previously activated cells (CD45RA, CD29, Leu-8), were measured on T lymphocytes recovered from blood and bronchoalveolar lavage fluid from normal subjects and patients with sarcoidosis. Few T lymphocytes from the lavage fluid of normal subjects and patients with sarcoidosis expressed the Leu 8+ or CD45RAbright phenotype expected for "naive" cells; more cells had the CD29dull phenotype expected for "naive" cells, though five of eight subjects had under 2% of such cells. These findings support the conclusion that the only T lymphocytes present on the surface of the respiratory tract are those recognising antigens that have been previously encountered by the individual. Further studies are required to determine whether "naive" T lymphocytes are present in other lung compartments.

Adult↗

Abnormal epithelial cells recovered by bronchoalveolar lavage: are they malignant?

The recovery of neoplastic cells by bronchoalveolar lavage is useful in the diagnosis of lung cancer. Abnormal epithelial cells can also be recovered from patients with interstitial lung diseases who do not have cancer, and therefore the usefulness of lavage in the diagnosis of malignancy in this setting is unknown. In this study, we evaluated the diagnostic significance of abnormal lavage cells recovered from patients with diffuse parenchymal abnormalities and compared the usefulness of standard cytologic assessment, correlation with clinical features, and immunocytochemical staining for carcinoembryonic antigen (CEA) in identifying abnormal cells that are truly malignant. Thirty of 2,314 patients had atypical lavage cells, but in only nine was lung cancer demonstrated. Although most patients with clinical suspicion of malignancy had lung carcinoma (six of seven), one such patient did not have cancer, and three were shown to have unsuspected carcinoma. Cytologic criteria identified definitely malignant cells in only four of nine patients with lung cancer, indicating that the approach is not sensitive. Immunostaining of abnormal cells with anti-CEA antibodies proved helpful. All patients with lung malignancy had CEA+ cells (n = 9), and no patient whose abnormal cells were CEA- proved to have cancer (n = 17). Because only nine of 13 patients with CEA+ cells had lung malignancy, the test is not diagnostic, but it appears to limit the need for further evaluation to a smaller group of patients in whom cancer is likely to be present. When used together, cytopathologic findings, detection of CEA by immunocytochemical techniques, and clinical correlates proved useful in diagnosis of lung malignancy, but further improvements are still needed to improve diagnostic accuracy.

Bronchoalveolar Lavage Fluid↗