Christopher H.S. Chan

Endobronchial tuberculosis : diagnostic features and therapeutic outcome

BACKGROUND Endobronchial tuberculosis (EBTB) is not seen often in the adult population. In most cases it is associated with pulmonary tuberculosis. During its course significant tracheobronchial stenosis may develop. In this study we report our experience with patients with EBTB. METHODS The records of 38 patients in whom EBTB had been proved by fibre optic bronchoscopy, microbiology and histology studies were evaluated. RESULTS Symptoms were non-specific and represented mainly the co-existing pulmonary tuberculosis. Signs characteristic of airway obstruction were rare (localized wheezing in 6%). Indications for bronchoscopy were radiographic features (87%), microscopy smear negatives (8%), wheezing (3%), and blood stained sputum (3%). The lesions were more likely to be seen in the main and upper bronchi. In 5% of patients the lower trachea was involved. Most lesions looked inflamed (51%), followed by caseous (19%), granulomatous (17%), ulcerative (12%), and fibrotic appearance (1%). The degree of stenosis was nil (22%), minor (45%), significant (13%), subtotal (13%), or total (7%). The patients were treated with a combination of antituberculosis drugs. Four patients underwent surgical procedures. Dilatation techniques were used in two patients for a right and left main bronchus stenosis respectively, with significant improvement in one. Dilatation in combination with laser therapy of a right intermediate bronchus stenosis did not result in re-expansion of the dependent part of the lung due to pleural adhesions. Left pneumonectomy was performed in one patient for destroyed lung. Twenty-two patients agreed to follow up bronchoscopy. The macroscopic appearance of the mucosa had improved in most cases but the degree of stenoses was unchanged in a considerable proportion (58%). Bronchial stenosis in one patient subsided during therapy but developed again at a later stage. CONCLUSIONS Patients with pulmonary tuberculosis and radiographic evidence of volume loss are recommended to undergo bronchoscopy to rule out EBTB. Specific symptoms for EBTB are rare. Biopsy of inflamed areas of bronchial mucosa seems to be indicated. Despite adequate antituberculosis therapy tracheobronchial stenosis may develop. Long term follow up including bronchoscopy seems therefore advocated. Dilatational intervention may be indicated in selected cases.

The effect of age on the presentation of patients with tuberculosis

OBJECTIVE To study the differences in presentation of young and elderly patients with tuberculosis (TB). DESIGN Between January 1991 and December 1992 all patients with TB diagnosed at the Department of Medicine, Prince of Wales Hospital, were recruited into the study. The following data were collected: body weight, coexisting medical problems, presenting symptoms, radiographic appearance, sputum results for acid-fast bacilli and peripheral blood biochemistry. The patients were divided into young ( < 65 years) and elderly ( > or = 65 years) age groups and differences in presentation of the 2 groups were analysed. RESULTS There were 78 young and 94 elderly patients with TB. The elderly patients had lower body weight, less haemoptysis but more non-specific complaints (25% vs 1%, P = 0.001). The chest radiographs in the elderly patients were less likely to have upper lobe infiltration (9% vs 37%, P = 0.0002) but more commonly had extensive infiltration of both lungs (17% vs 2%, P = 0.014). The only biochemical abnormality that was more common in the elderly was a low serum albumin level (64% vs 45%, P < 0.05). CONCLUSION Elderly patients with TB are more likely to present with non-specific complaints and atypical radiographic appearance. A high index of suspicion and prompt investigations in elderly patients may allow for earlier diagnosis and treatment of TB.

Proinflammatory Cytokine Levels in Patients with Lung Cancer and Carcinomatous Pleurisy

Increased levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) have been reported in various diseases, including lung cancer. The role of the soluble form of the IL-6 receptor (sIL-6R) remains to be explored. We therefore measured IL-6, IL-8 and sIL-6R in effusion fluid and blood serum of 10 lung cancer patients with carcinomatous pleurisy (5 men, 5 women, age 64.3 ± 4.4 years) by enzyme-linked immunosorbent assays. Serum levels of healthy individuals served as control. Concentrations of sIL-6R were much higher in serum compared to pleural effusion fluids of tumor patients (25,698 ± 1,993 vs. 9,438 ± 1,407 pg/ml; p < 0.0001). In contrast, IL-6 and IL-8 were found at high concentrations in carcinomatous pleural effusions in comparison to serum (IL-6: 964 ± 176 vs. 10.2 ± 1.3 pg/ml, p < 0.0001; IL-8: 319 ± 85 vs. 9.6 ± 9.6 pg/ml, p < 0.0001). The serum concentrations of IL-6 were not significantly increased in lung cancer patients (10.2 ± 1.3 pg/ml) in comparison to controls (7.3 ± 1.0 pg/ml). IL-8 was detected in the serum of only 1 patient and in low levels in the serum of controls (8.0 ± 1.5 pg/ml; all values are mean ± SEM). We conclude from this study that decreased levels of sIL-6R, but increased levels of IL-6 and IL-8, are found in pleural effusion fluid of patients with lung cancer and carcinomatous pleurisy. The low sIL-6R levels in the presence of high IL-6 levels in pleural effusions and the high sIL-6R levels in the presence of low IL-6 levels in serum may suggest a downregulation of sIL-6R expression or sIL-6R shedding in the presence of excessive amounts of IL-6.

Increase of both circulating Th1 and Th2 T lymphocyte subsets in IgA nephropathy

IgA nephropathy (IgAN), characterized by glomerular deposition of IgA and frequently elevated plasma IgA levels, has increased T helper cell activity. In vitro measurement of cytokines in supernatant of cultured peripheral lymphocytes revealed conflicting findings. We examined the profile of cytokine mRNA expressed in purified CD4+ cells in patients with IgAN in order to study their pattern of Th1 (releases IL‐2 and interferon‐gamma (IFN‐γ)) and Th2 (releases IL‐4 and IL‐5) T cell response. We assessed the circulating CD4+ T cells in patients and normal controls by the expression of messenger RNA (mRNA) for IL‐2, IL‐4, IL‐5 and IFN‐γ. The cytokine mRNAs were analysed with reverse transcription‐polymerase chain reaction and were measured semiquantitatively by using a housekeeping gene, β‐actin. Compared with the control subjects, CD4+ T lymphocytes from patients with IgAN expressed a higher level of IL‐2 mRNA (p=0.007), IFN‐γ mRNA (P = 0.04), IL‐4 mRNA (p = 0.048), and IL‐5 mRNA (P=0.016). Within these patients with IgAN, a good correlation was demonstrated between the gene expression of cytokines in Th1 or Th2 cells. The IL‐2 mRNA levels in Th1 cells from these patients with IgAN also correlated significantly with the IL‐4 or IL‐5 mRNA levels in their Th2 cells. Our study revealed IgAN is associated with activation in circulating lymphocytes of the IL‐2, IFN‐γ, IL‐4 and IL‐5 gene cluster, a pattern compatible with activation of both the Th1‐ and Th2‐like T lymphocyte population. The increased transcription of these cytokine genes may be contributory to the immunopathologic findings in IgAN.

Compartmentalization of pro-inflammatory cytokines in tuberculous pleurisy

Increased levels of interleukin-6 (IL-6) and IL-8 are found in various immunologically mediated inflammatory disorders. Concentrations of IL-6, IL-8 and the soluble form of the IL-6 receptor (sIL-6R) were determined in serum and effusion fluid of 25 patients with tuberculous pleurisy utilizing enzyme linked immunosorbent assays (EIA). Serum IL-6 levels were only slightly increased in patients with tuberculous pleurisy in comparison to controls (11.1 +/- 2.1 vs 7.3 +/- 1.0 pg ml-1). IL-8 could not be detected in the serum of tuberculosis patients, but it was detected in the serum of healthy controls (8.0 +/- 1.5 pg ml-1). In comparison to serum, IL-6 and IL-8 were found in high concentrations in pleural effusions (IL-6: 932 +/- 70 vs 11.1 +/- 2.1 pg ml-1, P < 0.0001; IL-8: 450 +/- 85 vs 0 +/- 0 pg ml-1). In contrast, sIL-6R concentrations were much higher in serum compared to pleural effusion levels [30,477 +/- 1905 vs 9881 +/- 1177 pg ml-1, P < 0.0001 (mean +/- SEM)]. The authors conclude that elevated levels of IL-6 and IL-8 in pleural effusions are compartmentalized at the site of active disease. The low levels of sIL-6R in the presence of high levels of IL-6 in pleural effusions, and the high levels of sIL-6R in the presence of low levels of IL-6 in serum suggest that the expression or shedding of sIL-6R may be downregulated in the presence of excessive amounts of IL-6.

Respiratory symptoms in elderly Chinese living in Hong Kong

Respiratory diseases can cause considerable disability in the elderly because of their limited respiratory reserve as a result of ageing. We have investigated the prevalence of respiratory symptoms and diseases in elderly Chinese in Hong Kong and compared these data with those in elderly Caucasian populations. Two thousand and thirty two (999 male and 1,033 female) subjects, selected by age-stratified random sampling from a register of Hong Kong residents aged 70 yrs and over were interviewed to complete a respiratory questionnaire. Total serum immunoglobulin E (IgE) was measured in 195 subjects. At least one respiratory symptom was reported by 56% of subjects. The most frequently reported symptoms were morning phlegm (26%), chronic cough with phlegm (10%) and wheeze in the past 12 months (8%). Of the self-reported diseases, the commonest was chronic bronchitis (7%), followed by asthma (5%), pulmonary tuberculosis (3%) and emphysema (2%). Of the 218 subjects with obstructive airway diseases, 128 (59%) had sought medical advice in the past 12 months. The most important determinants for respiratory symptoms and diseases were smoking and social class. Total serum IgE was significantly higher in current smokers than nonsmokers and also in those with chronic cough and phlegm than those without these complaints. Our study shows that respiratory ailments in Hong Kong elderly are as common as those reported in Sweden and the USA but less than those in England.

Absorption of lidocaine during aspiration anesthesia of the airway.

STUDY OBJECTIVE To determine the optimal solution to use when anesthetizing the airway by aspiration of lidocaine. DESIGN Randomized, double-blind clinical study. SETTING University hospital. PATIENTS 96 adult ASA physical status 1,II, and III patients, scheduled for diagnostic flexible bronchoscopy. INTERVENTIONS Patients were randomized to receive one of 5 solutions of lidocaine: Group A (n = 16): 1% lidocaine, 0.2 mL. kg(-1); Group B (n = 16): 1.5% 0.2 mL. kg(-1); Group C (n = 32): 2% 0.2 mL. kg(-1); Group D (n = 16): 1% 0.3 mL. kg(-1), and Group E (n = 16): 2% 0.3 mL. kg(-1). Fiberoptic bronchoscopy was performed after the airway was anesthetized with this aspiration technique, using the assigned lidocaine solution. The scope was manipulated in the trachea to test for anesthesia. MEASUREMENTS AND MAIN RESULTS Successful airway anesthesia was determined by tolerance to bronchoscopy without sustained coughing, and also by the number of lidocaine supplements, if any, that were given via the bronchoscope. Arterial plasma concentrations of lidocaine were measured in 33 patients from Groups C, D, and E. All solutions provided equally effective anesthesia of the airway. All patients tolerated endoscopy through the vocal cords, and 94 patients required no supplementary anesthesia, or only one dose of lidocaine, during bronchoscopy to the carina. The highest peak plasma concentrations of lidocaine were 5.02 and 6.28 microg. mL. No patient had signs of toxicity. CONCLUSIONS This technique produced anesthesia of the airway to the carina, safely, suitable for awake intubation, in 94 of 95 patients. The use of 1% lidocaine, 0.2 to 0.3 mL. kg(-1), so that the volume is 10 to 20 mL, is recommended.

Elevated interleukin-2 receptor level in patients with active pulmonary tuberculosis and the changes following anti-tuberculosis chemotherapy

Soluble interleukin-2 receptor (sIL-2R) is a marker of T-lymphocyte activation. We have undertaken a study to examine the serum sIL-2R levels in patients with pulmonary tuberculosis (TB) and the changes following anti-TB chemotherapy. Forty four patients with pulmonary TB or tuberculous pleural effusion were recruited. Serum was collected from the patients before and at 1, 2, 4 and 6 months after initiation of anti-TB chemotherapy. Serum sIL-2R level was measured by an enzyme immunoassay. The mean sIL-2R level before treatment was 1,452 +/- 103 (SEM) U.ml-1, which was significantly higher than that of healthy control subjects (374 +/- 30 U.ml-1). There was no significant change in the sIL-2R level at 1 month, but there was a gradual reduction from the second month onwards. At the sixth month the mean sIL-2R level was 1080 +/- 81 U.ml-1, which was significantly lower than that before treatment. However, despite clinical improvement, the sIL-2R levels at the sixth month were still significantly higher than those of control subjects. We conclude that sIL-2R levels were elevated in patients with pulmonary TB and there was a gradual reduction following anti-TB chemotherapy. However, the sIL-2R levels were still higher than control subjects at completion of treatment, suggesting a delayed resolution of the inflammation in patients with pulmonary TB.

Gene expression of interleukin‐3 and granuloeyte maerophage colony‐stimulating factor in circulating CD4+ T cells in acute severe asthma

Backgrouud Interleukin (IL)‐3 and granulocyte macrophage colony‐stimilating factor (GM‐CSF) may influence the inflammatory process in asthma through their regulatory role on eosinophil survival, differentiation and effector function.

Effect of Renal Transplantation on Pulmonary Function in Patients with End-Stage Renal Failure

Ten patients with end-stage renal failure on maintenance dialysis underwent serial lung function tests before and at monthly intervals after renal transplantation. Mean values of forced expiratory volume within 1 s, forced vital capacity, and total lung capacity were within the normal range before and up to 6, months after transplantation. The mean value of residual volume (RV) was above the normal range during all periods measured (157.8 +/- 21.5% predicted before transplantation and 121.2 +/- 17.0% predicted at 6 months after transplantation). No statistically significant changes in lung volumes were detected over a course of 6 months, but there was a trend for a reduction in RV after transplantation. The single-breath diffusion capacity for carbon monoxide (DLCO) was in the high-normal range before transplantation (115.7 +/- 9.5% predicted). It remained high at 1 month after transplantation (124.5 +/- 12.2% predicted), but it gradually came down to the normal range from the 2nd month onwards. At 6 months after transplantation the mean DLCO was 83.8 +/- 7.3% of predicted which was significantly (p < 0.0001) lower than the value before transplantation. We conclude that raised DLCO and RV values occurred in patients with end-stage renal failure on maintenance dialysis which were most likely the result of pulmonary vascular congestion, and these abnormalities tend to improve after renal transplantation.