Mechanisms of colchicine effect in the treatment of asbestosis and idiopathic pulmonary fibrosis.

The objective of this study was to evaluate the mechanisms of colchicine action in pulmonary fibrosis. The study included 10 patients with pulmonary fibrosis (idiopathic pulmonary fibrosis 5, asbestosis 4, and scleroderma 1) who had been admitted to Bellevue Hospital Center, a tertiary care public hospital in New York City. We administered colchicine 0.6 mg orally for 12 weeks to patients with pulmonary fibrosis. Symptoms, high resolution CT scans, pulmonary function tests, and bronchoalveolar lavage parameters were compared prior to and after treatment. Results showed declines in dyspnea index, selective improvement in several CT scans, but no statistically significant change in BAL cells, cytokines, fibronectin, or hydroxyproline. However, there was a decline in hydroxyproline in the BAL fluid in 8/10 patients. We concluded that colchicine has a mild antifibrotic effect which may be in inhibiting collagen formation since there was no effect on the inflammation that accompanies fibrosis.

Screening by specialists to reduce unnecessary test ordering in patients evaluated for tuberculosis.

STUDY OBJECTIVE: To determine if screening by specialists could reduce unnecessary test ordering and reduce costs related to diagnostic workup in patients undergoing evaluation for tuberculosis. DESIGN: Prospective evaluation of expert opinion in consecutive patients suspected of having tuberculosis. SETTING: A large municipal hospital. PATIENTS: Patients for whom sputum acid-fast smears were ordered. INTERVENTION: For patients from whom sputum acid-fast bacilli smears and cultures were requested, the chest radiograph and a brief clinical history were presented separately to two pulmonologists with considerable experience in tuberculosis. Each expert reviewed each case independently (and was blinded to the opinion of the other) and indicated if he thought sputum smear examination and culture was, in fact, necessary. Final clinical diagnosis and microbiological information were correlated with the experts' opinion. MEASUREMENTS AND MAIN RESULTS: Ninety-seven patients had sputum smears ordered and had chest radiographs available for review. The two experts believed that sputum examination (smear and culture) was indicated in only 51.5% and 52.6% of cases, respectively. Interobserver agreement was 84.4%. Ultimately, six cases of active tuberculosis were diagnosed. Each expert detected all proven cases of tuberculosis, although one case occurred in a patient with a poor quality radiograph about which the experts offered no opinion. CONCLUSIONS: Screening by experienced clinicians may be effective in reducing unnecessary test ordering and reducing costs related to diagnostic workup in patients evaluated for tuberculosis.

Isoniazid levels in the bronchoalveolar lavage fluid of patients with pulmonary tuberculosis.

Isoniazid (INH) is one of the most important first line drugs in the treatment of tuberculosis. We utilized high performance liquid chromatography with a hydrazone extraction technique to measure INH in bronchoalveolar lavage (BAL) fluid specimens from six patients with active pulmonary tuberculosis. We found BAL fluid INH levels to be similar to 2-h peak serum levels. The concentration of INH in BAL fluid from lobes with infiltrate was similar to the concentration of INH in BAL fluid from lobes without infiltrate (0.062 microgram/ml and 0.073 microgram/ml, respectively). After adjusting for protein concentration in the BAL fluid, INH levels in lobes with infiltrate were threefold lower than in lobes without infiltrate. The correlation between the concentration of INH in serum and BAL fluid approached significance after correcting for protein (lobes with infiltrate, r2 = 0.60 (p = 0.07); lobes without infiltrate, r2 = 0.50 (p = 0.12). INH penetrates into bronchoalveolar fluid, and concentrations of INH in the BAL fluid suggest that assessment of the INH serum concentration is adequate to evaluate bioavailability of the drug in patients with pulmonary tuberculosis.

Transbronchial needle aspiration (TBNA) in patients infected with HIV.

Transbronchial needle aspiration (TBNA) of intrathoracic lymph nodes has been shown to be useful in the diagnosis and staging of bronchogenic carcinoma. With the exception of sarcoidosis, the usefulness of TBNA has not been widely investigated in other clinical settings. We investigated the utility of TBNA with a 19-gauge histology needle in HIV-infected patients with mediastinal and hilar adenopathy at Bellevue Hospital Center. We performed 44 procedures in 41 patients. Adequate lymph node sampling was obtained in 35 of 44 (80%), and diagnostic material was obtained in 23 of 44 (52%) procedures. TBNA was the exclusive means of diagnosis in 13 of 41 (32%) patients. Of the 44 procedures, 23 (52%) were performed in patients with mycobacterial disease, with TBNA providing the diagnosis in 20 of 23 (87%). In these patients, positive TBNA specimens included smears of aspirated materials for acid-fast bacilli in 11, mycobacterial culture in 14, and histology in 15. In other diseases, TBNA diagnosed sarcoidosis with noncaseating granulomata in 2 of 4 patients and non-small cell lung cancer in 1 of 2 patients. TBNA was not helpful in other diseases including Pneumocystis carinii pneumonia, infection with Cryptococcus or Nocardia, bacterial pneumonia, viral pneumonia, and Kaposi's sarcoma. No pulmonary diagnosis was established in five patients. No complications of TBNA occurred. We conclude that TBNA through the flexible bronchoscope is safe and effective in the diagnosis of intrathoracic adenopathy in HIV-infected patients, and is particularly efficacious in the diagnosis of mycobacterial disease. Furthermore, TBNA may provide the only diagnostic specimen in almost one-third of HIV-infected patients, thereby sparing these patients more invasive procedures such as mediastinoscopy.

GM-CSF gene expression is normal but protein release is absent in a patient with pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by an excessive accumulation of surfactant lipids and proteins in the alveolar space. In mice with a homozygous deletion of granulocyte macrophage-colony stimulating factor (GM-CSF), their phenotype mimics PAP. To evaluate whether the knockout mouse model mimics human disease, we evaluated GM-CSF expression in alveolar macrophages from a patient with PAP. We performed multiple whole lung lavages on a patient with PAP, and cultured BAL cells in the presence or absence of LPS. In contrast to the GM-CSF knockout mouse, human BAL cells from a patient with PAP expressed mRNA for GM-CSF following LPS stimulation. However, similar to the knockout mouse, GM-CSF protein release from BAL cells was undetectable with or without LPS. BAL cells from normal human controls released GM-CSF in abundance after LPS stimulation. In BAL cells from the patient with PAP, neutralization of interleukin-10 (IL-10) by anti-IL-10 antibody, resulted in enhanced GM-CSF production. Thus, alveolar macrophages from a PAP lung have deficient GM-CSF production analogous to the GM-CSF knockout mice; in contrast, human cells from a PAP lung have an intact GM-CSF gene. This case report illustrates an important difference between the knockout mouse model of PAP and the human disease.

Pulmonary aspergilloma and AIDS. A comparison of HIV-infected and HIV-negative individuals.

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.

AIDS-related airway disease.

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.

Differentiation of the ILO boundary chest roentgenograph (0/1 to 1/0) in asbestosis by high-resolution computed tomography scan, alveolitis, and respiratory impairment.

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.

Basaloid-squamous cell carcinoma of the bronchus. Report of a case with review of the literature.

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.

Airways and lung: correlation of CT with fiberoptic bronchoscopy.

Recent advances in computed tomography (CT) and fiberoptic bronchoscopy (FOB) have led to confusion concerning the optimal use of these modalities, especially with regard to each other. The present review summarizes the current understanding of the role of CT in relation to FOB. Emphasis is placed on optimization of CT technique and basic principles of interpretation of the images. In addition, an in-depth evaluation is presented of the advantages and limitations of CT and FOB in the analysis of both focal and diffuse diseases of the airways and lung parenchyma.

Clinical utility of the polymerase chain reaction in the diagnosis of infections due to Mycobacterium tuberculosis.

OBJECTIVE: To evaluate the clinical utility of the polymerase chain reaction (PCR) in the diagnosis of infections due to Mycobacterium tuberculosis. DESIGN: Clinical specimens were assayed by PCR for the presence of the insertion element IS6110, a DNA sequence unique to the M tuberculosis complex of organisms. The PCR results were then correlated with acid-fast bacilli (AFB) smears, cultures, pathology, and clinical histories. SETTING: Bellevue Hospital, a large municipal teaching hospital. PATIENTS: Inpatients on the Bellevue Chest Service. MEASUREMENTS AND RESULTS: Sixty-five patients were evaluated. The PCR for M tuberculosis was positive in 37 patients and negative in 28. When correlated with smears, cultures, pathology, and clinical history, the sensitivity of PCR for a diagnosis of active tuberculosis (TB) was 100 percent. However, the specificity for a diagnosis of active TB was only 70 percent, as the PCR assay was positive in a number of patients with only prior, treated TB, or asymptomatic tuberculous infection. For a diagnosis of any TB infection (active, treated, or asymptomatic), sensitivity of PCR was 87.5 percent and specificity was 90 percent. CONCLUSIONS: The PCR assay for TB is extremely sensitive, but it lacks specificity for a diagnosis of active TB. Its role in clinical practice will likely be limited to well-defined situations, such as HIV-positive patients with intrathoracic adenopathy, and it may be most useful in excluding active TB from consideration in selected patients. Given the cost of the assay and the labor intensity it requires, it should not be part of the routine initial evaluation of patients with suspected pulmonary TB.

Hemoptysis: prospective high-resolution CT/bronchoscopic correlation.

The precise roles of fiberoptic bronchoscopy (FOB) and computed tomography (CT) of the chest in the evaluation of patients presenting with hemoptysis have not been clearly defined. On the assumption that both procedures would likely provide unique and complementary information, a prospective study with blinded interpreters using a modified high-resolution CT technique (HRCT) and FOB was designed to evaluate 57 consecutive patients admitted to Bellevue Hospital with hemoptysis. Etiologies included bronchiectasis (25 percent), tuberculosis (16 percent), lung cancer (12 percent), aspergilloma (12 percent), and bronchitis (5 percent): in an additional 5 percent of cases, hemoptysis proved to be due miscellaneous causes, while in 19 percent hemoptysis proved to be cryptogenic. Patients with lung cancer all were at least 50 years old, smoked an average of 78 pack-years, and had less severe hemoptysis but of longer duration. All had conditions diagnosed both by HRCT and FOB. High-resolution CT proved of particular value in diagnosing bronchiectasis and aspergillomas, while FOB was diagnostic of bronchitis and mucosal lesions such as Kaposi's sarcoma. Fiberoptic bronchoscopy localized bleeding in only 51 percent of cases. The high sensitivity of CT in identifying both the intraluminal and extraluminal extent of central lung cancers in conjunction with its value in diagnosing bronchiectasis suggest that CT should be obtained prior to bronchoscopy in all patients presenting with hemoptysis.