Peripheral immune response in pulmonary tuberculosis.

Cellular immune response and delayed-type hypersensitivity reactions are considered to play a major role in the immunopathogenesis of pulmonary tuberculosis (PTB). But the exact mechanism is still to be clarified. Th1 cells are mainly involved in cellular immune responses in PTB and provide a normal healing process with minimal or no sequela whereas Th2 cell and CD8(+) T lymphocyte responses may lead to more severe type of disease. In this study, we investigated the peripheral blood immune responses in PTB. The study group consisted of acid fast positive young male soldiers with PTB and a negative HIV serology. The control group included healthy young volunteer male soldiers without a history of PTB. Intracytoplasmic cytokine content of CD8(+) T cells and lymphocytes, including IL-2, IL-4, IL-5, IL-10 and IFN-gamma were determined by flow cytometry, and IL-2, IL-4, IL-5, IL-10, IFN-gamma and TNF-alpha serum levels were measured by cytometric bead array (CBA). No difference was observed between the percentages of T, B, NK cells and HLA-DR expression in both groups, however, the number of CD3(+)HLA-DR(+) activated T cell percentages was higher in PTB group as compared to healthy subjects. IL-2, IL-4, IL-5, IL-10 contents of lymphocytes and IFN-gamma(+)CD8(+) T cells were found to be significantly lower in PTB patients when compared with healthy subjects, and in parallel, serum IL-2, IL-4, IL-5 and TNF-alpha levels were also significantly lower in PTB patients. In conclusion we suggest that, CD8(+) T cells producing both Th1 and Th2 type cytokines, may play important role in the peripheral immune response to mycobacteria.

Does atopy affect the radiological extent of pulmonary tuberculosis?

BACKGROUND: Th1 cytokines, IL-2 and IFN-gamma , have critical importance in the CD4 cell driven antimycobacterial activity. Th2 type immune response is a characteristic feature of atopic disorders. Th1 and Th2 cells have been reported to negatively cross-regulate each other in vitro and in experimental animals. Our aim in the present study is to determine whether the atopy affects radiological extent of pulmonary tuberculosis (TB) and disease severity. MATERIALS AND METHODS: A total of 82 male patients with pulmonary TB were prospectively enrolled in the study between March 2005 and March 2006. All patients were evaluated for atopic symptoms and TB related systemic symptoms. Radiological dissemination was scored and cavitation was noted. The skin prick test (SPT) was performed and serum total IgE level was measured. RESULTS: The SPTs were positive in 28 of 82 (34.1 %) patients. There was no distinction between SPT-positive and negative patients in terms of pulmonary cavitation and radiological dissemination. The median IgE level of moderate-severe radiologically disseminated TB patients was significantly higher than that of mild radiologically disseminated TB patients (130 IU/ml vs. 58 IU/ml). Cavitary TB patients had also significantly higher median IgE levels (78 IU/ml vs. 46 IU/ml) (p < 0.05) CONCLUSION: This study suggests that SPT-positivity and atopic respiratory phenotype do not affect the formation of cavitation, radiological dissemination and systemic symptoms of pulmonary TB. The high level of IgE in patients with cavitary and radiologically disseminated TB may be a consequence of a dysregulated immune response to infection or reflect disease activity.

Does atopy affect the radiological extent of pulmonary tuberculosis?

Background: Th1 cytokines, IL-2 and IFN- , have critical importance in the CD4 cell driven antimycobacterial activity. Th2 type immune response is a characteristic feature of atopic disorders. Th1 and Th2 cells have been reported to negatively cross-regulate each other in vitro and in experimental animals. Our aim in the present study is to determine whether the atopy affects radiological extent of pulmonary tuberculosis (TB) and disease severity. Materials and methods: A total of 82 male patients with pulmonary TB were prospectively enrolled in the study between March 2005 and March 2006. All patients were evaluated for atopic symptoms and TB related systemic symptoms. Radiological dissemination was scored and cavitation was noted. The skinprick test (SPT) was performed and serum total IgE level was measured. Results: The SPTs were positive in 28 of 82 (34.1 %) patients. There was no distinction between SPT-positive and negative patients in terms of pulmonary cavitation and radiological dissemination.The median IgE level of moderate-severe radiologically disseminated TB patients was significantly higher than that of mild radiologically disseminated TB patients (130 IU/ml vs. 58 IU/ml). Cavitary TB patients had also significantly higher median IgE levels (78 IU/ml vs. 46 IU/ml) (p < 0.05) Conclusion: This study suggests that SPT-positivity and atopic respiratory phenotype do not affect the formation of cavitation, radiological dissemination and systemic symptoms of pulmonary TB. The high level of IgE in patients with cavitary and radiologically disseminated TB may be a consequence of a dysregulated immune response to infection or reflect disease activity

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Effect of active tuberculosis on skin prick allergy tests and serum IgE levels.

OBJECTIVE: Mycobacterium tuberculosis has been shown to suppress allergic airway disease driven by type 2 helper T cells in animal models. In this study, we investigated the effect of active tuberculosis on skin prick test (SPT) positivity and serum immunoglobulin (Ig) E levels of atopic patients with and without tuberculosis infection. MATERIALS AND METHODS: Seventeen atopic HIV-negative men with pulmonary tuberculosis and 18 atopic healthy male controls at our military hospital were studied prospectively between March 2005 and March 2006. The sums of all SPT positive tests and positivity to house dust mite alone were calculated before initiation of treatment and after 6 months. Measurement of total serum IgE levels was also performed at the same moments. RESULTS: The mean (SD) initial serum total IgE concentrations were significantly higher in the tuberculosis patients than in the healthy controls (324.1 [317.67] U/mL vs. 146.7 [75.29] U/mL, respectively; P < .05), The total serum IgE concentrations after 6 months of treatment were also higher in the patients than in the controls. The mean sum of SPT positivity was higher in the tuberculosis patients than in the controls at both testing times. CONCLUSION: Our study does not support the hypothesis that M tuberculosis suppresses atopy and atopic disorders, but large, prospective experimental studies are needed before excluding the possibility of a relationship.

Does the atopic phenotype prevent development of active tuberculosis infection?

This study investigated the relationship between the atopic phenotype and the development of active tuberculosis. A total of 82 human immunodeficiency virus negative males with active pulmonary tuberculosis and 88 healthy controls were enrolled into this prospective study. Serum immunoglobulin E (IgE) levels were measured and skin prick tests performed before initiation of treatment. Skin prick tests were positive in 34.1% of the tuberculosis patients and 39.8% of the controls. Allergic respiratory symptoms were significantly less frequent in skin prick test positive tuberculosis patients (21.4%) compared with skin prick test positive controls (62.9%). Median IgE levels in atopic tuberculosis patients were significantly higher than in atopic controls. The low rate of atopic respiratory complaints seen in the tuberculosis patients, despite having similar allergic skin prick test sensitivities to the controls, could be attributed to a weak T-helper (Th) 2 immune reaction and its effects on Th1-Th2 interaction.

Th1-Th2 interaction: is more complex than a see-saw?

Infections, such as tuberculosis, measles and diphtheria, may decrease the risk of developing atopic allergic disorders. Patients with pulmonary TB having similar allergic skin prick test sensitivity as healthy controls but unable to show vigorous atopic phenotype in their healthy period might be a sign for Th1-Th2 immune interaction.

The significance of elevated brain natriuretic peptide levels in chronic obstructive pulmonary disease.

We investigated the clinical significance of brain natriuretic peptide (BNP), a cardiac hormone, in chronic obstructive pulmonary disease (COPD). Subjects were 38 patients with stable COPD, of whom 20 had cor pulmonale (CP), and 22 were healthy individuals. Plasma BNP levels were measured and pulmonary arterial pressure (PAP) was estimated by echocardiography. Arterial blood gas analysis, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were also recorded. BNP levels of patients with COPD were higher than those of controls (48.2 +/- 37.5 and 9.3 +/- 3.0 pg/ml). Patients with CP had a higher mean BNP level with respect to those without CP (73.9 +/- 35.8 and 21.0 +/- 10.2 pg/ml, respectively). BNP levels correlated with PAP (r = 0.68), partial arterial oxygen pressure (r = -0.70), FEV1 (r = -0.65) and FVC (r = -0.52). We have concluded that BNP determination has a role in the diagnosis of CP in patients with COPD.

Low parathormone levels and hypercalcaemia in patients with pulmonary tuberculosis: relation to radiological extent of disease and tuberculin skin test.

AIM: We hypothesised that serum calcium (Ca) and parathormone (PTH) levels correlate with radiological extent and that there may also be a relationship between the tuberculin skin test (TST), serum Ca and PTH levels in patients with pulmonary tuberculosis (PTB). MATERIALS AND METHODS: Forty-four patients with active PTB and 33 healthy subjects were enrolled in the study. Serum Ca, PTH, magnesium and phosphate levels were measured in patients and controls and compared. Correlations were also investigated for TST values, erythrocyte sedimentation rate (ESR), the degree of radiological involvement, serum PTH and corrected Ca levels. RESULTS: There was a significant difference between the two groups for mean serum PTH and corrected Ca levels. Significant correlations were detected between radiological extent of disease and serum PTH levels, between TST values and serum PTH levels and between ESR and serum PTH levels. We suggest that abnormal Ca metabolism in PTB patients is related to the radiological extent of disease. Factors determining the radiological extent of disease, predominantly the patient's immune status, may have an important role in modulating Ca metabolism in PTB patients.

The incidence of tuberculosis in the armed forces: a good reflection of the whole population.

OBJECTIVE: Precise epidemiological data are essential to increase the efficiency of a tuberculosis (TB) control programme. In some countries significant numbers of TB cases go unrecorded or undetected. We aimed to investigate the incidence of TB in the Turkish Armed Forces (TAF), to obtain more reliable data on the entire population. DESIGN: In 2001, all soldiers with a new diagnosis of TB were enrolled in the study based on the official records of 14 military hospitals. The demographic data of the cases were evaluated. RESULTS: Six hundred and twenty-nine conscripts with TB were detected. Of these, 574 were aged between 20-24 years and 392 were smear-positive. The incidences of TB and smear-positive cases in TAF conscripts were calculated at respectively 76 and 47 per 100,000 population. When the age and sex distribution of the Turkish population and TB cases in Turkey were considered, the incidences of all TB and smear-positive TB in Turkey were estimated at respectively 33 and 17/100,000. These numbers are very close to those estimated by the World Health Organization. CONCLUSION: In countries where military service is compulsory and case detection rates are low, the TB incidence of the armed forces is a reliable reflection of the rate in the whole population.

Hemostatic changes in active pulmonary tuberculosis.

OBJECTIVE: Severe pulmonary tuberculosis (PTB) is sometimes complicated by deep vein thrombosis (DVT). We have searched for possible hemostatic disturbances that are predisposing factors for venous thrombosis in patients with PTB. DESIGN: Coagulation and platelet function tests were studied in 45 patients with active PTB and 20 healthy control volunteers before therapy. Findings were compared with results at 30 days. RESULTS: Analysis in patients with active PTB showed anemia, leucocytosis, thrombocytosis, elevation in plasma fibrinogen, factor VIII, plasminogen activator inhibitor 1 (PAI-1) with depressed antithrombin III (AT III) and protein C (PC) levels. On the 30th day of treatment, anemia, leucocytosis and thrombocytosis were improved. Fibrinogen and factor VIII levels had decreased to normal levels, PC and AT III levels had increased to normal levels, and there was no difference in PAI-1 levels. We found no activated protein C resistance. Platelet aggregation studies demonstrated increased platelet activation. However, DVT was not detected in patients during the follow-up period. CONCLUSION: Decreased AT III, PC and elevated plasma fibrinogen levels and increased platelet aggregation appear to induce a hypercoagulable state seen in PTB and improve with treatment.

Can't lung cancer patients detoxify procarcinogens?

BACKGROUND: Glutathione S-transferase mu (GST mu) enzyme detoxifies carcinogens in tobacco smoke. We assessed the clinical usefulness of serum assay of GSTm in determining the risk for lung cancer. MATERIALS AND METHODS: Fifty-nine patients with primary lung cancer and 32 control cases were enrolled. GSTm detection was performed by the method ELISA. RESULTS: GSTm enzyme positivity rate of the patient group (39%) was significantly lower than the control group (59.4%) (p < 0.05). The GSTm positivity rates were 28.6% for the non-smoker patients with a cancer history of relatives, 31.6% for the smoker patients with the cancer history of relatives, 14.6% for the non-smoker patients with the lung cancer history of relatives and 16.7% for the smoker patients with the lung cancer history of relatives. CONCLUSIONS: We concluded that if the people lacking GSTm are smokers and have a cancer and/or lung cancer history among their relatives, they would challenge a greater risk of lung cancer than the individuals having GST mu isoenzyme.

Morbid obesity in the medical ICU.

STUDY OBJECTIVE: To describe the clinical course, complications, and prognostic factors of morbidly obese patients admitted to the ICU compared to a control group of nonobese patients. DESIGN: A retrospective study. SETTING: Two university-affiliated hospitals. METHODS: We reviewed the medical records of 117 morbidly obese patients (body mass index >/= 40 kg/m(2)) admitted to the medical ICU between January 1994 and June 2000. Data collected included demographic information, comorbid condition, APACHE (acute physiology and chronic health evaluation) II score, invasive procedures, organ failure, and in-hospital mortality. RESULTS: Obstructive airway disease, pneumonia, and sepsis were the main reasons for admission to the ICU in the morbidly obese group. Sixty-one percent of the morbidly obese patients and 46% of the nonobese group required mechanical ventilation (p = 0.02). The mean lengths of mechanical ventilation and ICU stay were significantly longer for the morbidly obese group (7.7 +/- 9.6 days and 9.3 +/- 10.5 days vs 4.6 +/- 7.1 days and 5.8 +/- 8.2 days, respectively; p < 0.001). APACHE II scores were not significantly different in the two groups (19.1 +/- 7.6 and 20.6 +/- 12.2; p = 0.6). Overall mortality was 30% for the morbidly obese patients and 17% for the nonobese group (p = 0.019). By multivariate analysis, multiorgan failure (odds ratio [OR], 4.6; 95% confidence interval [CI], 2.1 to 16.6), PaO(2)/fraction of inspired oxygen < 200 for > 48 h (OR, 2.3; 95% CI, 1.2 to 7.8), and depressed left ventricular ejection fraction < 40% (OR, 1.4; 95% CI, 1.03 to 13.8) were independently associated with ICU mortality in the morbidly obese group. CONCLUSION: We conclude that critically ill morbidly obese patients are at increased risk of morbidity and mortality compared to the nonobese patients.

Skeletal muscle dysfunction in chronic obstructive pulmonary disease.

It has become increasingly recognized that skeletal muscle dysfunction is common in patients with chronic obstructive pulmonary disease (COPD). Muscle strength and endurance are decreased, whereas muscle fatigability is increased. There is a reduced proportion of type I fibers and an increase in type II fibers. Muscle atrophy occurs with a reduction in fiber cross-sectional area. Oxidative enzyme activity is decreased, and measurement of muscle bioenergetics during exercise reveals a reduced aerobic capacity. Deconditioning is probably very important mechanistically. Other mechanisms that may be of varying importance in individual patients include chronic hypercapnia and/or hypoxia, nutritional depletion, steroid usage, and oxidative stress. Potential therapies include exercise training, oxygen supplementation, nutritional repletion, and administration of anabolic hormones.

A comparison of severity of illness scoring systems for elderly patients with severe pneumonia.

OBJECTIVE: To evaluate the predictive ability of three severity of illness scoring systems in elderly patients with severe pneumonia requiring mechanical ventilation compared to a younger age group. DESIGN: Prospective cohort study. SETTING: Two university-affiliated tertiary care hospitals. PATIENTS AND PARTICIPANTS: One hundred four patients 75 years of age and older and 253 patients younger than 75 years of age enrolled from medical intensive care units. MEASUREMENTS AND RESULTS: Probabilities of hospital death for patients were estimated by the Acute Physiology and Chronic Health Evaluation (APACHE) II, the Mortality Probability Model (MPM) II and the Simplified Acute Physiology Score (SAPS) II. Predicted risks of hospital death were compared with observed outcomes using three methods of assessing the overall goodness of fit. The actual mortality of the elderly group was 54.87 % (95 % confidence interval [CI]: 45.2-64.4 %) compared to 28.9 % (95 % CI, 23.3-34.4 %) in the younger age group. There was a significant difference in the predictive accuracy of the scoring systems as assessed by the c-index, which is equivalent to the area under the receiver operator characteristics (ROC) curve, between the two groups, but not within individual groups. Calibration was insufficient for APACHE II and SAPS II in the elderly cohort as in-hospital mortality was lower than the predicted mortality for both models. CONCLUSIONS: Although the three severity of illness scoring systems (APACHE II, MPM II and SAPS II) demonstrated average discrimination when applied to estimate hospital mortality in the elderly patients with severe pneumonia, MPM II had the closest fit to our database. Alternative modeling approaches might be needed to customize the model coefficients to the elderly population for more accurate probabilities or to develop specialized models targeted to the designed population.