TIOtropium Safety and Performance In Respimat® (TIOSPIRTM ): Analysis of Asian cohort of COPD patients.

BACKGROUND AND OBJECTIVE: The TIOtropium Safety and Performance In Respimat (TIOSPIR) trial showed similar safety and exacerbation efficacy profiles for tiotropium Respimat and HandiHaler in patients with COPD. The TIOSPIR results for patients in Asia are presented here. METHODS: TIOSPIR evaluated once-daily tiotropium Respimat 5 and 2.5 µg with HandiHaler 18 µg in patients with COPD. Primary endpoints included time to death and time to first COPD exacerbation. Safety and exacerbation efficacy profiles were determined for the Asian region, and for Asia (all treatment arms pooled) versus the rest of the world (RoW). RESULTS: In Asia (n = 2356), time to death was similar for Respimat 5 and 2.5 µg versus HandiHaler 18 µg (hazard ratio (HR) (95% CI): 0.96 (0.67, 1.38) and 1.23 (0.87, 1.73)). Risk of COPD exacerbation was similar for Respimat 5 µg, but increased for 2.5 µg versus HandiHaler 18 µg (HR (95% CI): 0.99 (0.85, 1.15) and 1.17 (1.00, 1.35)). Time to death in Asia and RoW was similar (HR (95% CI): 1.15 (0.99, 1.35)). Time to first COPD exacerbation was longer (HR (95% CI): 0.84 (0.78, 0.89)) and exacerbation rates were lower in Asia, but severe exacerbations were more frequent than in the RoW. Risk of major adverse cardiovascular events was similar for both regions. CONCLUSION: Similar safety and exacerbation efficacy profiles were observed for tiotropium Respimat 5 µg and HandiHaler 18 µg in patients with COPD from Asia, analogous to the global analysis. Asian patients had lower risk of, and fewer exacerbations overall, but a higher proportion of severe exacerbations than in the RoW.

Efficacy of tiotropium in COPD patients from Asia: a subgroup analysis from the UPLIFT trial.

BACKGROUND AND OBJECTIVE: Studies in respiratory diseases other than chronic obstructive pulmonary disease suggest potentially differing responses to medications among patients from different regions. We report a subgroup analysis of patients recruited to Asian centres from a previously reported 4-year COPD trial. METHODS: Subgroup analysis from a randomized, double-blinded, placebo-controlled trial of tiotropium 18 µg daily in COPD. Primary end-point was rate of decline in FEV(1) . Secondary end-points included spirometry at individual time points, health-related quality of life (St George's Respiratory Questionnaire), exacerbations and mortality. RESULTS: Of 5992 patients, 362 were from Asian centres (100 from Japan). Mean age 66 years, 95% men, 13% current smokers, BMI: 21 kg/m(2) ; post-bronchodilator FEV(1) : 44% predicted; St George's Respiratory Questionnaire total score: 44 units. No treatment effect was observed for rate of decline in FEV(1) although annual decline was less in Asian patients. Morning pre-bronchodilator FEV(1) and forced vital capacity improved in Asian patients (P < 0.05). Tiotropium reduced number of exacerbations (rate ratio (95% confidence interval (CI)): 0.73 (0.57-0.94)). Hazard ratios (95%CI) for exacerbations and hospitalized exacerbations (tiotropium/control) were 0.81 (0.62-1.05) and 0.85 (0.61-1.19), respectively. St George's Respiratory Questionnaire total score improved by 1.5-6.1 units (P < 0.05 for months 18, 24, 30 and 36) with tiotropium. Fatal events occurred in 34 tiotropium (18.5%) and 42 control (23.6%) patients. CONCLUSIONS: In COPD patients from Asia, tiotropium improves lung function, improves health-related quality of life and reduces exacerbations over 4 years of treatment.

Roflumilast in Asian patients with COPD: A randomized placebo-controlled trial.

BACKGROUND AND OBJECTIVE: Roflumilast, an oral, selective phosphodiesterase 4 inhibitor, has been shown to reduce exacerbations and improve pulmonary function in patients with COPD. This study examined the efficacy, safety and tolerability of roflumilast in Asian patients with COPD. METHODS: Patients with COPD were randomized 1:1 to enter a 12-week treatment period and receive either oral roflumilast, 500 µg once daily, or placebo, following a single-blind, 4-week baseline period in which all patients received placebo. The primary end point was mean change in FEV1 from baseline to each postrandomization visit during the treatment period. Other spirometric lung function measurements were evaluated as secondary end points. COPD exacerbations were monitored. Safety was assessed from clinical laboratory tests, vital signs, physical examination (including electrocardiogram) and monitoring of adverse events (AEs). RESULTS: Of 551 patients recruited, 410 were randomized and received at least one dose of study medication (roflumilast, n = 203; placebo, n = 207). Superiority of roflumilast over placebo was demonstrated by a statistically significant difference in postbronchodilator FEV1 (79 mL, P < 0.0001). Other spirometry end points, including prebronchodilator FEV1, pre-and postbronchodilator FEV6, forced vital capacity and peak expiratory flow significantly favoured roflumilast over placebo. AEs were more common with roflumilast than with placebo, but were comparable with those reported in previous studies. CONCLUSIONS: Roflumilast, 500 µg once daily, improves pulmonary function in Asian patients with COPD. The safety and tolerability of roflumilast in this population was similar to that in a Caucasian population.

Trends in COPD mortality and hospitalizations in countries and regions of Asia-Pacific.

BACKGROUND AND OBJECTIVE: The growing burden of COPD in the Asia-Pacific region supports the need for more intensive research and analysis of the epidemiology of COPD to raise awareness of the disease and its causes, to ensure the development of effective national health policies and to facilitate equitable deployment of finite health-care resources in the prevention and management of COPD. This study estimated and compared COPD mortality and hospital morbidity rates and trends in these rates over time across countries and regions of Asia-Pacific. METHODS: Data consistent with standard definitions of COPD (ICD-9/ICD-10) for the period 1991-2004 were obtained from national health statistics agencies. For countries/regions with complete national mortality and hospitalization data (Australia, Pacific Canada (British Columbia, Hong Kong, South Korea and Taiwan), annual age-standardized mortality and hospitalization rates were calculated for men and women aged >or= 40 years. Negative binomial regression modelling was used to estimate rate ratios for country/region, gender and age differences and general trends over time. RESULTS: Mortality rates per 10,000 population ranged 6.4-9.2 in men, 2.1-3.5 in women and 3.7-5.3 overall in 2003. Corresponding ranges for morbidity were 32.6-334.7, 21.2-129 and 28.1-207.3 per 10 000. Trend analysis of data since 1997 produced annual percentage changes in mortality versus hospitalization of -4.4% versus -0.7% in Australia, -3.6% versus 7.5% in Pacific Canada (British Columbia), -7.15% versus -5.6% in Hong Kong and -2.9% versus -4.2% in Taiwan. CONCLUSIONS: In Asia-Pacific, overall mortality and morbidity rates are high and trends in mortality and morbidity vary between countries/regions. Differences in rates and trends for men and women most likely reflect the different trends in historical and prevalent smoking profiles for COPD in the different countries and regions.

Effectiveness of influenza vaccination in prevention of influenza-like illness among inhabitants of old folk homes.

The aims of the study were to determine the attack rate of influenza-like illness among inhabitants of five old folk homes nationwide using influenza vaccine as a probe and the effectiveness of influenza vaccination in prevention of influenza-like illness. We conducted a nonrandomized, single-blind placebo control study from June 2003 to February 2004. VAXIGRIP(R) 2003 Southern hemisphere formulation was used. Among 527 subjects, the attack rates of influenza-like illness in the influenza vaccine group were 6.4, 4.6 and 2.4% during the first, second and third 2-month periods, respectively. The attack rates of influenza-like illness in the placebo group were 17.7, 13.8 and 10.1%. Influenza vaccination reduced the risk of contracting influenza-like illness by between 14, and 45%. The vaccine effectiveness in reducing the occurrence of influenza-like illness ranged from 55 to 76%, during the 6-month study followup. The presence of cerebrovascular diseases significantly increased the risk of influenza-like illness (p < 0.005). Vaccine recipients had fewer episodes of fever, cough, muscle aches, runny nose (p < 0.001) and experience fewer sick days due to respiratory illness. Subjects who received influenza vaccination had clinically and statistically significant reductions in the attack rate of influenza-like illness. Our data support influenza vaccination of persons with chronic diseases and >50 year olds living in institutions.

Application of phase congruency for discriminating some lung diseases using chest radiograph.

A novel procedure using phase congruency is proposed for discriminating some lung disease using chest radiograph. Phase congruency provides information about transitions between adjacent pixels. Abrupt changes of phase congruency values between pixels may suggest a possible boundary or another feature that may be used for discrimination. This property of phase congruency may have potential for deciding between disease present and disease absent where the regions of infection on the images have no obvious shape, size, or configuration. Five texture measures calculated from phase congruency and Gabor were shown to be normally distributed. This gave good indicators of discrimination errors in the form of the probability of Type I Error (δ) and the probability of Type II Error (ß). However, since 1 - δ is the true positive fraction (TPF) and ß is the false positive fraction (FPF), an ROC analysis was used to decide on the choice of texture measures. Given that features are normally distributed, for the discrimination between disease present and disease absent, energy, contrast, and homogeneity from phase congruency gave better results compared to those using Gabor. Similarly, for the more difficult problem of discriminating lobar pneumonia and lung cancer, entropy and homogeneity from phase congruency gave better results relative to Gabor.

Whole-genome sequencing to establish relapse or re-infection with Mycobacterium tuberculosis: a retrospective observational study.

BACKGROUND: Recurrence of tuberculosis after treatment makes management difficult and is a key factor for determining treatment efficacy. Two processes can cause recurrence: relapse of the primary infection or re-infection with an exogenous strain. Although re-infection can and does occur, its importance to tuberculosis epidemiology and its biological basis is still debated. We used whole-genome sequencing-which is more accurate than conventional typing used to date-to assess the frequency of recurrence and to gain insight into the biological basis of re-infection. METHODS: We assessed patients from the REMoxTB trial-a randomised controlled trial of tuberculosis treatment that enrolled previously untreated participants with Mycobacterium tuberculosis infection from Malaysia, South Africa, and Thailand. We did whole-genome sequencing and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) typing of pairs of isolates taken by sputum sampling: one from before treatment and another from either the end of failed treatment at 17 weeks or later or from a recurrent infection. We compared the number and location of SNPs between isolates collected at baseline and recurrence. FINDINGS: We assessed 47 pairs of isolates. Whole-genome sequencing identified 33 cases with little genetic distance (0-6 SNPs) between strains, deemed relapses, and three cases for which the genetic distance ranged from 1306 to 1419 SNPs, deemed re-infections. Six cases of relapse and six cases of mixed infection were classified differently by whole-genome sequencing and MIRU-VNTR. We detected five single positive isolates (positive culture followed by at least two negative cultures) without clinical evidence of disease. INTERPRETATION: Whole-genome sequencing enables the differentiation of relapse and re-infection cases with greater resolution than do genotyping methods used at present, such as MIRU-VNTR, and provides insights into the biology of recurrence. The additional clarity provided by whole-genome sequencing might have a role in defining endpoints for clinical trials. FUNDING: Wellcome Trust, European Union, Medical Research Council, Global Alliance for TB Drug Development, European and Developing Country Clinical Trials Partnership.

Impact of connecting tuberculosis directly observed therapy short-course with smoking cessation on health-related quality of life.

BACKGROUND: With evolving evidence of association between tuberculosis (TB) and tobacco smoking, recommendations for the inclusion of tobacco cessation interventions in TB care are becoming increasingly important and more widely disseminated. Connecting TB and tobacco cessation interventions has been strongly advocated as this may yield better outcomes. However, no study has documented the impact of such connection on health-related quality of life (HRQoL). The objective of this study was to document the impact of an integrated TB directly observed therapy short-course (DOTS) plus smoking cessation intervention (SCI) on HRQoL. METHODS: This was a multi-centered non-randomized controlled study involving 120 TB patients who were current smokers at the time of TB diagnosis in Malaysia. Patients were assigned to either of two groups: the usual TB-DOTS plus SCI (SCIDOTS group) or the usual TB-DOTS only (DOTS group). The effect of the novel strategy on HRQoL was measured using EQ-5D questionnaire. Two-way repeated measure ANOVA was used to examine the effects. RESULTS: When compared, participants who received the integrated intervention had a better HRQoL than those who received the usual TB care. The SCIDOTS group had a significantly greater increase in EQ-5D utility score than the DOTS group during 6 months follow-up (mean ± SD = 0.98 ± 0.08 vs. 0.91 ± 0.14, p = 0.006). Similarly, the mean scores for EQ-VAS showed a consistently similar trend as the EQ-5D indices, with the scores increasing over the course of TB treatment. Furthermore, for the EQ-VAS, there were significant main effects for group [F (1, 84) = 4.91, p = 0.029, η2 = 0.06], time [F (2, 168) = 139.50, p = < 0.001, η2 = 0.62] and group x time interaction [F (2, 168) = 13.89, p = < 0.001, η2 = 0.14]. CONCLUSIONS: This study supports the evidence that an integrated TB-tobacco treatment strategy could potentially improve overall quality of life outcomes among TB patients who are smokers.

Satisfaction levels and asthma control amongst Malaysian asthmatic patients on budesonide/formoterol maintenance and reliever therapy: experience in a real-life setting.

BACKGROUND: Budesonide/formoterol used for both maintenance and reliever therapy has been shown to benefit patients with persistent asthma. We evaluated patient satisfaction and asthma control among Malaysian patients prescribed budesonide/formoterol as single maintenance and reliever therapy in a real-life clinical practice. METHODS: Adult patients diagnosed with partially controlled or uncontrolled asthma were recruited in a 6-month, prospective, open-label study involving ten hospital-based chest clinics in Malaysia. Patients were prescribed one or two inhalations of budesonide/formoterol Turbuhaler (160/4.5 µg per inhalation) twice daily as maintenance therapy and additional inhalation as reliever therapy. Maintenance doses were decided by physicians based on Global Initiative for Asthma-defined treatment objectives. The primary outcome measure was the change in mean Satisfaction with Asthma Treatment Questionnaire (SATQ) scores from baseline to an average of 3 months and 6 months. Secondary outcome was the change in mean Asthma Control Questionnaire 5-item version (ACQ-5) scores from baseline to an average of 3 months and 6 months and the proportion of patients achieving the minimum clinically important difference. RESULTS: Of 201 eligible patients recruited, 195 completed the study. Overall, SATQ mean (standard deviation) score was significantly improved from 5.1 (0.76) at baseline to 5.5 (0.58) (P < 0.001). The increase was observed in all domains of SATQ and had occurred at 3 months for most patients. ACQ-5 mean (standard deviation) score was significantly reduced from 2.2 (1.13) at baseline to 1.2 (0.95) (P < 0.001). A total of 132 (67.7.1%) patients had achieved the minimal clinically important difference (≥0.5) of ACQ-5 scores at study end. CONCLUSION: In a nationwide study, budesonide/formoterol maintenance and reliever therapy achieved greater patient satisfaction and better asthma control compared with previous conventional asthma regimes among Malaysian patients treated in a real-life practice setting. Such an approach may represent an important treatment alternative for our local patients with persistent asthma.

The SCIDOTS Project: evidence of benefits of an integrated tobacco cessation intervention in tuberculosis care on treatment outcomes.

BACKGROUND: There is substantial evidence to support the association between tuberculosis (TB) and tobacco smoking and that the smoking-related immunological abnormalities in TB are reversible within six weeks of cessation. Therefore, connecting TB and tobacco cessation interventions may produce significant benefits and positively impact TB treatment outcomes. However, no study has extensively documented the evidence of benefits of such integration. SCIDOTS Project is a study from the context of a developing nation aimed to determine this. METHODS: An integrated TB-tobacco intervention was provided by trained TB directly observed therapy short-course (DOTS) providers at five chest clinics in Malaysia. The study was a prospective non-randomized controlled intervention using quasi-experimental design. Using Transtheoretical Model approach, 120 eligible participants who were current smokers at the time of TB diagnosis were assigned to either of two treatment groups: conventional TB DOTS plus smoking cessation intervention (integrated intervention or SCIDOTS group) or conventional TB DOTS alone (comparison or DOTS group). At baseline, newly diagnosed TB patients considering quitting smoking within the next 30 days were placed in the integrated intervention group, while those who were contemplating quitting were assigned to the comparison group. Eleven sessions of individualized cognitive behavioral therapy with or without nicotine replacement therapy were provided to each participant in the integrated intervention group. The impacts of the novel approach on biochemically validated smoking cessation and TB treatment outcomes were measured periodically as appropriate. RESULTS: A linear effect on both 7-day point prevalence abstinence and continuous abstinence was observed over time in the intervention group. At the end of 6 months, patients who received the integrated intervention had significantly higher rate of success in quitting smoking when compared with those who received the conventional TB treatment alone (77.5% vs. 8.7%; p < 0.001). Furthermore, at the end of TB treatment (6 months or later), there were significantly higher rates of treatment default (15.2% vs. 2.5%; p = 0.019) and treatment failure (6.5% vs. 0%; p = 0.019) in the DOTS group than in the SCIDOTS group. CONCLUSION: This study provides evidence that connecting TB-tobacco treatment strategy is significant among TB patients who are smokers. The findings suggest that the integrated approach may be beneficial and confer advantages on short-term outcomes and possibly on future lung health of TB patients who quit smoking. This study may have important implications on health policy and clinical practice related to TB management among tobacco users.

Tobacco use prevalence, knowledge, and attitudes among newly diagnosed tuberculosis patients in Penang State and Wilayah Persekutuan Kuala Lumpur, Malaysia.

BACKGROUND: There is sufficient evidence to conclude that tobacco smoking is strongly linked to tuberculosis (TB) and a large proportion of TB patients may be active smokers. In addition, a previous analysis has suggested that a considerable proportion of the global burden of TB may be attributable to smoking. However, there is paucity of information on the prevalence of tobacco smoking among TB patients in Malaysia. Moreover, the tobacco-related knowledge, attitudes, and behaviors of TB patients who are smokers have not been previously explored. This study aimed to document the prevalence of smoking among newly diagnosed TB patients and to learn about the tobacco use knowledge and attitudes of those who are smokers among this population. METHODS: Data were generated on prevalence rates of smoking among newly diagnosed TB patients in the State of Penang from January 2008 to December 2008. The data were obtained based on a review of routinely collated data from the quarterly report on TB case registration. The study setting comprised of five healthcare facilities (TB clinics) located within Penang and Wilayah Persekutuan, Kuala Lumpur health districts in Malaysia, which were involved in a larger project, known as SCIDOTS Project. A 58-item questionnaire was used to assess the tobacco use knowledge, attitudes and behaviors of those TB patients who were smokers. RESULTS: Smoking status was determinant in 817 of 943 new cases of TB from January to December 2008. Of this, it was estimated that the prevalence rates of current- and ex-smoking among the TB patients were 40.27% (329/817) and 13.95% (114/817), respectively. The prevalence of ever-smoking among patients with TB was estimated to be 54,220 per 100,000 population. Of 120 eligible participants for the SCIDOTS Project, 88 responded to the survey (73.3% response rate) and 80 surveys were analyzed (66.7% usable rate). The mean (+/- SD) total score of tobacco use knowledge items was 4.23 +/- 2.66 (maximum possible score=11). More than half of the participants (51.3%) were moderately dependent to nicotine. A moderately large proportion of the respondents (41.2%) reported that they have ever attempted to quit smoking, while more than half (56.3%) have not. Less than half (47.5%) of the study participants had knowledge about the body system on which cigarette smoking has the greatest negative effect. The majority wrongly believed that smokeless tobacco can increase athletic performance (60%) and that it is a safe and harmless product (46.2%). An overwhelming proportion (>80%) of the patients believed that: smoking is a waste of money, tobacco use is very dangerous to health, and that smokers are more likely to die from heart disease when compared with non-smokers. The use of smokeless tobacco was moderately prevalent among the participants with 28.8% reporting ever snuffed, but the use of cigar and pipe was uncommon. CONCLUSION: Smoking prevalence rate is high among patients with TB in Malaysia. These patients generally had deficiencies in knowledge of tobacco use and its health dangers, but had positive attitudes against tobacco use. Efforts should be geared towards reducing tobacco use among this population due to its negative impact on TB treatment outcomes.