Yee-Tang Wang

Tuberculosis treatment effect on T-cell interferon-γ responses to Mycobacterium tuberculosis-specific antigens

The hypothesis that T-cell interferon-&ggr; responses to Mycobacterium tuberculosis-specific antigens decline as disease activity diminishes with tuberculosis (TB) treatment has generated interest in the interferon-&ggr; release assays (IGRAs) as treatment-monitoring tools. We studied the effect of TB treatment on these responses as measured by the QuantiFERON-TB® Gold In-tube (QFT-IT) and T-SPOT.TB® assays. 275 sputum culture-positive, HIV-uninfected pulmonary TB patients were tested with QFT-IT and T-SPOT.TB® at baseline, treatment completion and 6 months thereafter. The QFT-IT was also performed at the end of the intensive phase. The time-treatment effect on the qualitative and quantitative IGRA results was determined. There were significant declines in the positivity rates and quantitative results of both IGRAs with treatment. The QFT-IT positivity rate was significantly lower than the T-SPOT.TB®. The test reversion rate was significantly different for the two assays (13.9% for T-SPOT.TB® versus 39.2% for QFT-IT). 79% and 46% tested positive with T-SPOT.TB® and QFT-IT respectively at 6 months post-treatment completion. The kinetics of the quantitative responses was not significantly different between subjects with and without risk factors for disease relapse. That a substantial proportion of patients remained test-positive after TB treatment would suggest a limited role of IGRAs as treatment monitoring tools.

Maximal respiratory pressures in adult Chinese, Malays and Indians

Maximal static inspiratory and expiratory mouth pressures (PI,max and PE,max, respectively) enable the noninvasive measurement of global respiratory muscle strength. The aim of this study was primarily to obtain normal values of PI,max and PE,max for adult Chinese, Malays and Indians and, secondarily, to study their effect on lung volumes in these subjects. Four hundred and fifty two healthy subjects (221 Chinese, 111 Malays, 120 Indians) were recruited. Measurements of PI,max from residual volume (RV), PE,max from total lung capacity (TLC) and forced vital capacity (FVC) were obtained in the seated position. There were significant ethnic differences in PI,max and PE,max measurements obtained in males, and FVC measurements in both males and females. Chinese males had higher PI,max values (mean (+/-SD) 88.7+/-32.5 cmH2O) and higher PE,max values (113.4+/-41.5) than Malay males (PI,max 74.0+/-22.7 cmH2O, PE,max 94.7+/-23.4 cmH2O). Chinese males had higher PE,max than Indian males (PI,max = 83.7+/-30.0 cmH2O, PE,max 98.4+/-29.2 cmH2O). There were no significant differences among Chinese females (PI,max 53.6+/-2.3 cmH2O, PE,max 68.3+/-24.0 cmH2O), Malay females (PI,max 50.7+/-18.3 cmH2O, PE,max 63.6+/-21.6 cmH2O) and Indian females (PI,max 50.0+/-15.2 cmH2O, PE,max 60.7+/-20.4 cmH2O). In both sexes, the Chinese had a higher FVC compared with Malays and Indians. After adjusting for age, height and weight, race was still a determinant for PE,max in males, and FVC in both sexes. The FVC only correlated weakly with PI,max and PE,max in both sexes. Ethnic differences in respiratory muscle strength, and lung volumes, occur among Asians. However, respiratory muscle strength does not explain the differences in lung volumes in healthy Asian subjects.

Use of a T Cell Interferon‐γ Release Assay to Evaluate Tuberculosis Risk in Newly Qualified Physicians in Singapore Healthcare Institutions

BACKGROUND Surveillance for latent tuberculosis in high-risk groups such as healthcare workers is limited by the nonspecificity of the tuberculin skin test (TST) in BCG-vaccinated individuals. The Mycobacterium tuberculosis antigen-specific interferon-gamma release assays (IGRAs) show promise for more accurate latent tuberculosis detection in such groups. OBJECTIVE To compare the utility of an IGRA, the T-SPOT.TB assay, with that of the TST in healthcare workers with a high rate of BCG vaccination. METHODS Two hundred seven medical students from 2 consecutive cohorts underwent the T-SPOT.TB test and the TST in their final year of study. Subjects with negative baseline test results underwent repeat testing after working for 1 year as junior physicians in Singapores public hospitals. RESULTS The baseline TST result was an induration 10 mm or greater in diameter in 177 of the 205 students who returned to have their TST results evaluated (86.3%), while the baseline T-SPOT.TB assay result was positive in 9 (4.3%) of the students. Repeat T-SPOT.TB testing in 182 baseline-negative subjects showed conversion in 9 (4.9%). A repeat TST in 18 subjects with baseline-negative TST results did not reveal any TST result conversion. CONCLUSIONS The high rate of positive baseline TST results in our BCG-vaccinated healthcare workers renders the TST unsuitable as a surveillance tool in this tuberculosis risk group. Use of an IGRA has enabled the detection and treatment of latent tuberculosis in this group. Our T-SPOT.TB conversion rate highlights the need for greater tuberculosis awareness and improved infection control practices in our healthcare institutions.

A new asthma severity index: a predictor of near-fatal asthma?

Bronchial hyperresponsiveness (BHR), measured as the provocative dose of inhaled histamine or methacholine required to produce a 20% fall in forced expiratory volume in one second (FEV1) (PD20), is widely used as one of the indices of asthma severity. Excessive bronchoconstriction, reflected by the maximal percentage fall in forced vital capacity (FVC) at PD20 (deltaFVC %) during BHR testing, is considered to be the most important pathophysiological determinant in fatal asthma. The present study hypothesized that an index which combines both the ease of airway narrowing and excessive bronchoconstriction, deltaFVC %/log(PD20), may be better in assessing asthma severity, especially in those at risk of near-fatal attacks. The dose-response curves of 46 asthmatics who underwent methacholine challenge testing were studied. Group 1 (n=14) patients had mild disease, Group 2 (n=21) had moderate disease and Group 3 (n=11) had severe disease, as classified according to the Global Initiative for Asthma. Nine patients had prior intubation for near-fatal asthma. deltaFVC %/log (PD20) was better than deltaFVC % and PD20 in categorizing patients into the three severity groups (p<0.0001), but more importantly, it was able to discriminate patients with previous intubation from those without (p=0.04). It also correlated better with FEV1 (% predicted), frequency of symptoms and inhaled steroid requirement than either index alone. It is concluded that the percentage fall in forced vital capacity/log of the provocative dose causing a 20% fall in forced expiratory volume in one second combines information on the ease and excessive degrees of airway narrowing in asthma. This new index may be better at assessing asthma severity and in discriminating those at risk of near-fatal attacks.

Characteristics of patients with delayed diagnosis of infectious pulmonary tuberculosis.

Objective:  The aim of this study was to identify patient and disease characteristics associated with delayed diagnosis of infectious pulmonary tuberculosis (TB).

Interferon-γ responses to Mycobacterium tuberculosis-specific antigens in diabetes mellitus

To the Editor: Although diabetes mellitus has long been recognised as a risk factor for tuberculosis, it was only recently that strong evidence for this emerged [1]. Persons with diabetes mellitus have a two or three times higher risk of developing tuberculosis disease than nondiabetics; those with tuberculosis and diabetes mellitus have a four times higher risk of death during tuberculosis treatment and a higher risk of tuberculosis relapse [2, 3]. Diabetics therefore constitute a target group in whom the identification of latent tuberculosis infection (LTBI) and its treatment may potentially be an important strategy for tuberculosis elimination [4, 5]. Interferon-γ release assays (IGRAs) are immunodiagnostic tests for identification of LTBI. These tests have shown superior specificity and positive predictive value for progression to active disease over the tuberculin skin test [6–9]. Although the IGRAs do not distinguish active from latent tuberculosis [10, 11], they are often done as part of the work-up for active tuberculosis in cases where diagnostic uncertainty exists. To date, there is scant information in the literature regarding the performance of these assays in diabetics. In a previous report in which we evaluated the T-SPOT. TB (Oxford Immunotec, Abingdon, UK) and QuantiFERON In-Tube (QFT-IT) (Cellestis, Melbourne, Australia) assays in a head-to-head manner in 270 culture-confirmed pulmonary tuberculosis patients, we had found undiminished sensitivity of these assays in the presence of diabetes mellitus [12]. Walsh et al. [13] have also reported that diabetes did not affect the performance of the second-generation QuantiFERON TB Gold (QFT-G) and T-SPOT. TB …

Use of bilevel positive airway pressure ventilatory support for pathological flail chest complicating multiple myeloma

Multiple myeloma is a common disease that universally involves the skeletal system. Although rib involvement may occur, the development of pathological flail chest is rare. We describe the treatment and course of this condition in an elderly female, and the use of the bilevel positive airway pressure (BiPAP) ventilatory system in providing pneumatic stabilization, while definitive chemotherapy was given to heal the pathological fractures. Our experience with this patient suggests that, despite its dramatic clinical manifestation, the association of flail chest with multiple myeloma may not predict a poor prognosis. We have also found that pneumatic stabilization can be achieved by using the bilevel positive airway pressure ventilatory support through a tracheostomy.

Dietary Cholesterol Increases the Risk whereas PUFAs Reduce the Risk of Active Tuberculosis in Singapore Chinese

BACKGROUND Experimental studies suggest that cholesterol enhances the intracellular survival of Mycobacterium tuberculosis, whereas marine ω-3 (n-3) and ω-6 (n-6) fatty acids (FAs) may modulate responses to M. tuberculosis in macrophage and animal models. However, there are no epidemiologic data from prospective studies of the relation between dietary cholesterol and FAs and the risk of developing active tuberculosis. OBJECTIVE We aimed to investigate the relation between dietary intake of cholesterol and FAs and the risk of active tuberculosis in a prospective cohort in Singapore. METHODS We analyzed data from the Singapore Chinese Health Study, a cohort of 63,257 Chinese men and women aged 45-74 y recruited between 1993 and 1998. Dietary intake of cholesterol and FAs was determined with the use of a validated food-frequency questionnaire. Incident cases of active tuberculosis were identified via linkage with the nationwide tuberculosis registry. Analysis was performed with the use of Cox proportional hazards models. RESULTS As of 31 December 2013, 1136 incident cases of active tuberculosis were identified. Dietary cholesterol was positively associated with an increased risk of active tuberculosis in a dose-dependent manner. Compared with the lowest intake quartile, the HR was 1.22 (95% CI: 1.00, 1.47) for the highest quartile (P-trend = 0.04). Conversely, dietary marine n-3 and n-6 FAs were associated with a reduced risk of active tuberculosis in a dose-dependent manner. Compared with the lowest quartile, the HR for the highest intake quartile was 0.77 (95% CI: 0.62, 0.95) for marine n-3 FAs (P-trend = 0.01) and 0.82 (95% CI: 0.68, 0.98) for n-6 FAs (P-trend = 0.03). There was no association with saturated, monounsaturated, or plant-based n-3 FA intake. CONCLUSION Dietary intake of cholesterol may increase the risk of active tuberculosis, whereas marine n-3 and n-6 FAs may reduce the risk of active tuberculosis in the Chinese population.

The shorter multidrug-resistant tuberculosis treatment regimen in Singapore: are patients from South-East Asia eligible?

Multidrug-resistant tuberculosis (MDR-TB) is a major public health challenge, with an estimated 480 000 new cases emerging globally each year [1]. Treatment success rates using the 20-month conventional World Health Organization (WHO) regimen have been low, being about 52% in 2013 [1]. Observational studies in Bangladesh and several African countries have shown success rates of 84% using a shorter regimen [2–4]. Based on these studies, in May 2016 the WHO conditionally recommended a standardised, shorter 9–12-month regimen for MDR pulmonary tuberculosis (PTB), comprising a 4–6-month intensive phase with a combination of kanamycin, moxifloxacin, prothionamide, clofazimine, pyrazinamide, high-dose isoniazid and ethambutol, followed by a 5-month continuation phase containing moxifloxacin, clofazimine, ethambutol and pyrazinamide [5]. Confirmed resistance (except to isoniazid) or suspected ineffectiveness to a drug in this regimen is one of the exclusion criteria [5]. About 30% of MDR pulmonary-TB patients in a SE Asian (Singaporean) sample are eligible for the WHO shorter regimen http://ow.ly/KF3330dMSVs

Lung elastic recoil in normal young adult Chinese compared with Caucasians

Chinese people have smaller total lung capacity (TLC) compared with Caucasians of similar age, sex and height. One possible reason would be a higher lung elastic recoil in Chinese. Most published values for lung elastic recoil viz static lung compliance (CLst), shape constant K, and maximal static transpulmonary pressure (PLmax) have been from Caucasian subjects. The aim of our study was to obtain values for lung elastic recoil in normal young adult Chinese subjects. Static expiratory pressure-volume (P-V) curves were studied in 22 healthy Chinese subjects (12 males and 10 females). The P-V curve was fitted using an iterative least mean squares regression on a computer, according to an exponential equation: V = A-Be-KP, where V is lung volume, P is transpulmonary pressure, and A, B and K are constants. Mean values +/- SD for K, CLst and PLmax were 0.12 +/- 0.04, 230 +/- 103 ml.cmH2O-1 and 27.5 +/- 7.5 cmH2O, respectively. The values of CLst and K were similar to that of normal Caucasian subjects, whereas values of PLmax were lower. We attributed the lower PLmax partly to weaker inspiratory muscles in Chinese compared with Caucasians. We conclude that lung elastic recoil in normal young adult Chinese is similar to that of healthy young adult Caucasians. Hence, lung elasticity is unlikely to explain the racial differences in static lung volumes.Chinese people have smaller total lung capacity (TLC) compared with Caucasians of similar age, sex and height. One possible reason would be a higher lung elastic recoil in Chinese. Most published values for lung elastic recoil viz static lung compliance (CLst), shape constant K, and maximal static transpulmonary pressure (PLmax) have been from Caucasian subjects. The aim of our study was to obtain values for lung elastic recoil in normal young adult Chinese subjects. Static expiratory pressure-volume (P-V) curves were studied in 22 healthy Chinese subjects (12 males and 10 females). The P-V curve was fitted using an iterative least mean squares regression on a computer, according to an exponential equation: V = A-Be-KP, where V is lung volume, P is transpulmonary pressure, and A, B and K are constants. Mean values +/- SD for K, CLst and PLmax were 0.12 +/- 0.04, 230 +/- 103 ml.cmH2O-1 and 27.5 +/- 7.5 cmH2O, respectively. The values of CLst and K were similar to that of normal Caucasian subjects, whereas values of PLmax were lower. We attributed the lower PLmax partly to weaker inspiratory muscles in Chinese compared with Caucasians. We conclude that lung elastic recoil in normal young adult Chinese is similar to that of healthy young adult Caucasians. Hence, lung elasticity is unlikely to explain the racial differences in static lung volumes.