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Phage T4 early promoters are resistant to inhibition by the anti-sigma factor AsiA.

Phage T4 early promoters are transcribed in vivo and in vitro by the Escherichia coli RNA polymerase holoenzyme Esigma(70). We studied in vitro the effects of the T4 anti-sigma(70) factor AsiA on the activity of several T4 early promoters. In single-round transcription, promoters motB, denV, mrh.2, motA wild type and UP element-deleted motA are strongly resistant to inhibition by AsiA. The alpha-C-terminal domain of Esigma(70) is crucial to this resistance. DNase I footprinting of Esigma(70) and Esigma(70)AsiA on motA and mrh.2 shows extended contacts between the holoenzyme with or without AsiA and upstream regions of these promoters. A TG --> TC mutation of the extended -10 motif in the motA UP element-deleted promoter strongly increases susceptibility to inhibition by AsiA, but has no effect on the motA wild-type promoter: either the UP element or the extended -10 site confers resistance to AsiA. Potassium permanganate reactivity shows that the two structure elements are not equivalent: with AsiA, the motA UP element-deleted promoter opens more slowly whereas the motA TC promoter opens like the wild type. Changes in UV laser photoreactivity at position +4 on variants of motA reveal an analogous distinction in the roles of the extended -10 and UP promoter elements.

Bacteriophage T4↗

The bacteriophage T4 inhibitor and coactivator AsiA inhibits Escherichia coli RNA Polymerase more rapidly in the absence of sigma70 region 1.1: evidence that region 1.1 stabilizes the interaction between sigma70 and core.

The N-terminal region (region 1.1) of sigma70, the primary sigma subunit of Escherichia coli RNA polymerase, is a negatively charged domain that affects the DNA binding properties of sigma70 regions 2 and 4. Region 1.1 prevents the interaction of free sigma70 with DNA and modulates the formation of stable (open) polymerase/promoter complexes at certain promoters. The bacteriophage T4 AsiA protein is an inhibitor of sigma70-dependent transcription from promoters that require an interaction between sigma70 region 4 and the -35 DNA element and is the coactivator of transcription at T4 MotA-dependent promoters. Like AsiA, the T4 activator MotA also interacts with sigma70 region 4. We have investigated the effect of region 1.1 on AsiA inhibition and MotA/AsiA activation. We show that sigma70 region 1.1 is not required for MotA/AsiA activation at the T4 middle promoter P(uvsX). However, the rate of AsiA inhibition and of MotA/AsiA activation of polymerase is significantly increased when region 1.1 is missing. We also find that RNA polymerase reconstituted with sigma70 that lacks region 1.1 is less stable than polymerase with full-length sigma70. Our previous work has demonstrated that the AsiA-inhibited polymerase is formed when AsiA binds to region 4 of free sigma70 and then the AsiA/sigma70 complex binds to core. Our results suggest that in the absence of region 1.1, there is a shift in the dynamic equilibrium between polymerase holoenzyme and free sigma70 plus core, yielding more free sigma70 at any given time. Thus, the rate of AsiA inhibition and AsiA/MotA activation increases when RNA polymerase lacks region 1.1 because of the increased availability of free sigma70. Previous work has argued both for and against a direct interaction between regions 1.1 and 4. Using an E. coli two-hybrid assay, we do not detect an interaction between these regions. This result supports the idea that the ability of region 1.1 to prevent DNA binding by free sigma70 arises through an indirect effect.

DNA, Bacterial↗

Drug problem in southeast and southwest Asia.

In 2002, the drug problem in Southeast and Southwest Asia was serious, particularly in the production of opium and heroin in Afghanistan, Myanmar, and Laos, the three largest producers of illicit opium in the world. The increasing illicit manufacture of ATS, particularly methamphetamine, in Southeast Asia, mainly in China and Myanmar, was also a major concern. Some reports indicated that ephedrine, used for illicitly producing methamphetamine in Southeast Asia, is diverted and smuggled out of China and India, whereas caffeine, the adulterant used for producing methamphetamine tablets, is mainly smuggled into Myanmar through its border with Thailand. Seizure data showed a dramatic increase in trafficking in MDMA through Southeast Asia. In terms of the drug epidemic, in 2002, cannabis remained overall the main drug of abuse in all of the countries of Southeast and Southwest Asia. Opiates, mainly opium and heroin, were also the drugs of choice except in Thailand, where opiate abuse declined, but ATS was the main drug of abuse due to its low cost and availability. A significant increase in ATS abuse, amphetamine, methamphetamine, and MDMA among the youth who smoked, sniffed, and inhaled them was reported in Cambodia, China, Indonesia, Laos, Myanmar, the Philippines, and Thailand. Injecting drug use among opiate abusers has been identified as the prime cause of the rapid spread of HIV/AIDS in Southeast and Southwest Asia.

Asia, Southeastern↗

Estimating the burden of road traffic injuries among children and adolescents in urban South Asia.

Over a million people died from road traffic injuries (RTI) globally in the year 2000 and as many as 50 million were injured. Yet there has been little work focused on the South Asia region, let alone the vulnerable segments of population such as children and adolescents. This study aims at measuring the burden of disease caused by urban road traffic injuries among children and adolescents in South Asia. This study selected 26 studies for review and data extraction out of 1505 published articles. Data from the studies were pooled to calculate the proportion and characteristics of child and adolescent RTI, regional RTI incidence and mortality rates, and an estimate of the burden of disease caused by these injuries through the use of the healthy life years lost (HeaLY) composite measure. Our findings showed that the majority of injuries occurred in males (67-80%) and the most frequent age group injured was between ages 0 and 9 representing 40% of cases. Children and adolescents represent an average of 22% of all those with RTI whom seek care. Children and adolescents represented an average of 13% of all RTI deaths. Regional RTI incidence rate was calculated at 880 per 100,000 urban persons aged 0-19. Mortality due to RTI was at 17 deaths per 100,000 urban persons aged 0-19 in South Asia. Burden of disease was calculated 16 HeaLYs per 1000 general population from road traffic mortality alone. With disability data added, then 27.7 HeaLYs per 1000 general population are lost from road traffic injuries in South Asia. The increasing burden of RTI in young persons in South Asia is a call for considering appropriate research and effective interventions. This relatively high loss of healthy life from RTI needs to be addressed by public health systems in South Asia.

Accidents, Traffic↗

Neutralization antigenic sites on type Asia-1 foot-and-mouth disease virus defined by monoclonal antibody-resistant variants.

Seven neutralizing monoclonal antibodies (nMAbs) produced against serotype Asia-1 foot-and-mouth disease virus (FMDV) were used to select neutralization-resistant variants. Seven single and six multiple antibody-resistant variants were selected to identify neutralization antigenic sites on FMDV Asia-1. The variants no longer reacted with nMAbs which were used to select them when tested by microneutralization test (MNT), radioimmunoassay (RIA) and agar gel immunodiffusion (AGID) assay. Based on the binding and neutralization patterns of the variants, the nMAbs could be divided into discrete groups indicating the presence of three independent antigenic sites with evidence for occurrence of possibly a fourth site on the virus surface. Site 1 was present on 140S, 12Sps and VP1 and thus was conformation-independent. Sites 2 and 3 were restricted to the intact virion (140S) and thus were more conformation-dependent. Site 4 present on 140S virions and 12S protein subunits was less conformation-dependent. The site 3 nMAbs neutralized the infectivity of all the ten different Asia-1 virus isolates tested indicating that this site is conserved in Asia-1 virus serotype. Both cross-neutralization of different Asia-1 viruses with the nMAbs and cross-inhibition assays between MAbs demonstrated that the nMAbs recognized at least six different epitopes on Asia-1 virus.

Animals↗

Suicide and mental disorders in Asia.

Sixty one percent of the suicides in the world occur in Asia. The suicide rate of Asia has been calculated as 12.6/100,000. This is an underestimate as data is unavailable for 20.7% of the Asian population. Population-based studies on suicide in Asia reveal that 68-97% had diagnosable psychiatric disorders. Only 35-40% of suicides in India and China received the diagnosis of depression. The association between depression and suicide is less pronounced in Asia. Demographic and socio-cultural risk factors for suicide in Asia are different from Western countries but clinical factors appear to be more similar than different. Suicide is a major public and mental health problem in Asia and there is an urgent need to develop effective national suicide prevention strategy in Asian countries.

Alcoholism↗

Y-Chromosome evidence for a northward migration of modern humans into Eastern Asia during the last Ice Age.

The timing and nature of the arrival and the subsequent expansion of modern humans into eastern Asia remains controversial. Using Y-chromosome biallelic markers, we investigated the ancient human-migration patterns in eastern Asia. Our data indicate that southern populations in eastern Asia are much more polymorphic than northern populations, which have only a subset of the southern haplotypes. This pattern indicates that the first settlement of modern humans in eastern Asia occurred in mainland Southeast Asia during the last Ice Age, coinciding with the absence of human fossils in eastern Asia, 50,000-100,000 years ago. After the initial peopling, a great northward migration extended into northern China and Siberia.

Africa↗

Paternal population history of East Asia: sources, patterns, and microevolutionary processes.

Asia has served as a focal point for human migration during much of the Late Pleistocene and Holocene. Clarification of East Asia's role as a source and/or transit point for human dispersals requires that this region's own settlement history be understood. To this end, we examined variation at 52 polymorphic sites on the nonrecombining portion of the Y chromosome (NRY) in 1,383 unrelated males, representing 25 populations from southern East Asia (SEAS), northern East Asia (NEAS), and central Asia (CAS). The polymorphisms defined 45 global haplogroups, 28 of which were present in these three regions. Although heterozygosity levels were similar in all three regions, the average pairwise difference among haplogroups was noticeably smaller in SEAS. Multidimensional scaling analysis indicated a general separation of SEAS versus NEAS and CAS populations, and analysis of molecular variance produced very different values of Phi(ST) in NEAS and SEAS populations. In spatial autocorrelation analyses, the overall correlogram exhibited a clinal pattern; however, the NEAS populations showed evidence of both isolation by distance and ancient clines, whereas there was no evidence of structure in SEAS populations. Nested cladistic analysis demonstrated that population history events and ongoing demographic processes both contributed to the contrasting patterns of NRY variation in NEAS and SEAS. We conclude that the peopling of East Asia was more complex than earlier models had proposed-that is, a multilayered, multidirectional, and multidisciplinary framework is necessary. For instance, in addition to the previously recognized genetic and dental dispersal signals from SEAS to NEAS populations, CAS has made a significant contribution to the contemporary gene pool of NEAS, and the Sino-Tibetan expansion has left traces of a genetic trail from northern to southern China.

Animals↗

Diversity of the envelope glycoprotein among human immunodeficiency virus type 1 isolates of clade E from Asia and Africa.

Human immunodeficiency virus type 1 isolates of clade E, known to be largely responsible for the fulminating epidemic in Southeast Asia, have been derived exclusively from Asia and Africa. Here we provide full or partial sequences of the envelope glycoprotein gene from 13 additional clade E isolates from Asia representing patients in both early and late stages of disease. More extensive comparison of isolates within clade E by geographic locale, stage of disease, and year of isolation is now possible. The genetic diversity of clade E isolates from Asia, particularly among those derived from early-stage patients, is restricted compared with African isolates (mean interisolate distances in gp120, 5.4 and 20.2%, respectively). However, patients hospitalized with AIDS-related illnesses in Thailand harbored clade E isolates exhibiting broader interisolate diversity and with highly heterogeneous third hypervariable loop sequences. An additional pair of cysteine residues, predicting a novel disulfide bridge and present in 80% of clade E isolates from Asia, was uniformly absent from six African isolates. Clade E isolates in Thailand from early-stage subjects continue to be genetically similar to potential vaccine prototype strains, providing a favorable environment for the evaluation of genotype E candidate vaccines. However, evidence of increasing interisolate diversity is appearing among late-stage patients in Asia. This diversification of the clade E virus, if sustained, may impact preventive vaccine development strategies.

Africa↗

Survival rates of invasive breast cancer among ethnic Chinese women born in East Asia and the United States.

BACKGROUND: Few studies have compared the breast cancer survival rates of US born ethnic Chinese women and the survival rates of Chinese immigrants. The main purpose of this study is to explore the difference of breast cancer survival rates between the two populations and compare the survival rates to those of Caucasians born in the US. METHODS: Between 1973 and 2002, 365,215 women who had been diagnosed with primary invasive breast cancer (ICD-O-2 C500:C509) were recorded in the Surveillance, Epidemiology, and End Results (SEER) registries. Of the 316,881 breast cancer patients who were white, 180,835 (57%) were born in the United States, 20,983 (7%) were born elsewhere, and 115,063 (36%) had unknown birthplaces. Among the 3,634 breast cancer patients who were ethnically Chinese, 952 (26%) patients were born in the US, 1,356 (37%) were born in East Asia, 146 (4%) were born elsewhere, and 1,180 (33%) had unknown birthplaces. We compared the survival rates and estimated the risk ratios (RRs) by the Kaplan-Meier estimates and the Cox proportional hazards models. RESULTS: A lower 5-year overall survival rate of breast cancer was observed among Chinese women born in East Asia (0.74, 95% CI=0.72-0.77) than those born in the U.S. (0.79, 95% CI=0.76-0.81), with an adjusted hazards ratio of 1.22 (95% CI=1.06-1.40). The 5-year survival rates for SEER stage were higher among Chinese women born in the U.S. (localized: 0.90, 95% CI=0.87-0.93; regional: 0.71, 95% CI=66-0.77; distant: 0.16, 95% CI=0.06-0.25) than that among Chinese women born in East Asia (localized: 0.86, 95% CI=0.83-0.89; regional: 0.68, 95% CI=0.63-0.73; distant: 0.16, 95% CI=0.07-0.25). Higher 5-year survival rates among Chinese women born in the U.S. in comparison to Chinese women born in East Asia were also observed in different calendar years (1973-1980, 1981-1990, 1991-2002), in surgery and radiation therapy. CONCLUSIONS: Our analysis showed that among the Chinese breast cancer patients, women born in East Asia had lower 5-year survival rates than women born in the United States. SEER stage, grade, and tumor size appear to be important prognostic factors. The poor 5-year survival rates among Chinese women born in East Asia indicate potential problems of accessing medical facilities for early detection, diagnosis and treatment because of potential language and culture barriers, lower education level, as well as stress of the first generation of migrant Chinese women in the United States.

Adult↗

The bacteriophage T4 AsiA protein: a molecular switch for sigma 70-dependent promoters.

The AsiA protein, encoded by bacteriophage T4, inhibits Esigma70-dependent transcription at bacterial and early-phage promoters. We demonstrate that the inhibitory action of AsiA involves interference with the recognition of the -35 consensus promoter sequence by host RNA polymerase. In vitro experiments were performed with a C-terminally labelled sigma factor that is competent for functional holoenzyme reconstitution. By protease and hydroxyl radical protein footprinting, we show that AsiA binds region 4.2 of sigma70, which recognizes the -35 sequence. Direct interference with the recognition of the promoter at this locus is supported by two parallel experiments. The stationary-phase sigma factor containing holoenzyme, which can initiate transcription at promoters devoid of a -35 region, is insensitive to AsiA inhibition. The recognition of a galP1 promoter by Esigma70 is not affected by the presence of AsiA. Therefore, we conclude that AsiA inhibits transcription from Escherichia coli and T4 early promoters by counteracting the recognition of region 4.2 of sigma70 with the -35 hexamer.

Amino Acid Sequence↗

The interaction between the AsiA protein of bacteriophage T4 and the sigma70 subunit of Escherichia coli RNA polymerase.

The AsiA protein of bacteriophage T4 binds to the sigma70 subunit of Escherichia coli RNA polymerase and plays a dual regulatory role during T4 development: (i) inhibition of host and phage early transcription, and (ii) coactivation of phage middle-mode transcription, which also requires the T4 DNA binding transcriptional activator, MotA. We report that the interaction between AsiA and sigma70 occurs with a 1:1 stoichiometry. When preincubated with RNA polymerase, AsiA is a potent inhibitor of open complex formation at the lac UV5 promoter, whereas it does not perturb preformed open or intermediate promoter complexes. DNase I footprinting and electrophoretic mobility shift analyses of RNA polymerase-DNA complexes formed at the T4 early promoter P15.0 show that AsiA blocks the initial RNA polymerase binding step that leads to the formation of specific closed promoter complexes. A contrasting result is obtained on the T4 middle promoter PrIIB2, where AsiA stimulates the formation of both closed complexes and open complexes. Therefore, we propose that AsiA modulates initial DNA binding by the RNA polymerase, switching promoter usage at the level of closed complex formation.

Bacterial Proteins↗

Construct validity and dimensional structure of the ASIA motor scale.

BACKGROUND/OBJECTIVE: The use of the American Spinal Injury Association (ASIA) motor score as an outcome measure requires metrological study. This paper tests the hypothesis that a more accurate representation of motor function is obtained using separate upper and lower extremity scales rather than combining all 20 key muscle ratings into a single ASIA motor score. METHODS: We analyzed archived data from 6116 ASIA motor scale records extracted from the National Spinal Cord Injury Statistical Center Database. RESULTS: The hypothesis that separate scales more accurately represent motor function than a single motor scale was supported (chi2(difference) = 2596; df=1; P < 0.0001). Two scales account for 87% of the variance, whereas a single scale accounts for only 82%. Lower extremity function is well represented in both solutions; however, upper extremity function is accurately represented only with the use of 2 separate scales. CONCLUSIONS: The use of components of the ASIA standards for other than classification of spinal cord injury needs study. Several lines of study converge to provide strong support for the existence of 2 distinctive dimensions underlying the ASIA motor scale. The use of a single motor score in spinal cord injury research should be questioned and justified to the extent possible. The use of upper and lower extremity scales will lead to a reduction in measurement error when the motor score is used as an outcome measure. The confirmation of 2 separate dimensions underlying the ASIA motor score will enable more accurate representation of motor function in spinal cord injury research.

Adolescent↗

The asiA gene product of bacteriophage T4 is required for middle mode RNA synthesis.

The asiA gene of bacteriophage T4 encodes a 10-kDa peptide which binds strongly in vitro to the sigma 70 subunit of Escherichia coli RNA polymerase, thereby weakening sigma 70-core interactions and inhibiting sigma 70-dependent transcription. To assess the physiological role of this protein, we have introduced an amber mutation into the proximal portion of the asiA gene. On suppressor-deficient hosts, this mutant phage (amS22) produces minute plaques and exhibits a pronounced delay in phage production. During these mutant infections, T4 DNA synthesis is strongly delayed, suggesting that the AsiA protein plays an important role during the prereplicative period of phage T4 development. The kinetics of protein synthesis show clearly that while T4 early proteins are synthesized normally, those expressed primarily via the middle mode exhibit a marked inhibition. In fact, the pattern of protein synthesis after amS22 infection resembles greatly that seen after infection by amG1, an amber mutant in motA, a T4 gene whose product is known to control middle mode RNA synthesis. The amber mutations in the motA and asiA genes complement, both for phage growth and for normal kinetics of middle mode protein synthesis. Furthermore, primer extension analyses show that three different MotA-dependent T4 middle promoters are not recognized after infection by the asiA mutant phage. Thus, in conjunction with the MotA protein, the AsiA protein is required for transcription activation at T4 middle mode promoters.

Bacteriophage T4↗

Serological comparison of type Asia 1 foot and mouth disease virus isolates from Thailand.

Antigenic variation of type Asia 1 foot and mouth disease (FMD) virus in Thailand was examined using a total of 50 field viruses isolated between 1986 and 1992. A two-dimensional serum neutralisation test was used to calculate r values for comparison of these isolates with a reference vaccine strain, Asia 1 Bangkok 1960 (BKK/60). Viruses were also compared to two field isolates, Asia 1 36-2/88 and Asia 1 45/88, and some were compared to another vaccine strain, Asia 1 Nakhon Pathom 1984 (NPT/84). In 80% of cases, field isolates were deemed to be significantly different from the vaccine virus Asia 1 BKK/60, and the distribution of r values indicated that there would be some advantage in selecting a new vaccine strain more closely related to contemporary field strains.

Animals↗

Cholesterol, coronary heart disease, and stroke in the Asia Pacific region.

BACKGROUND: Cholesterol levels in many Asian countries are rising. Predictions of the likely effects of this on the incidence of cardiovascular diseases have mostly relied on data from Western populations. Whether the associations between total cholesterol and cardiovascular diseases are similar in Asia is not established. METHODS: The Asia Pacific Cohort Studies Collaboration (APCSC) is an individual-participant data meta-analysis of prospective studies from the Asia-Pacific region. Cox models were applied to the combined data from 29 cohorts to estimate the region-, sex-, and age-specific hazard ratios of major cardiovascular diseases by the fifths of total cholesterol. RESULTS: At baseline, the age/sex-adjusted mean value of total cholesterol was higher in Australia and New Zealand (ANZ) (5.52 +/- 1.05 mmol/l) than in Asia (4.87 +/- 1.05 mmol/l). During 2 million person-years of follow-up among 352 033 individuals, 4841 cardiovascular deaths were recorded. The association of total cholesterol with coronary heart disease and stroke was similar in Asian and ANZ cohorts. Overall, each 1-mmol/l higher level of total cholesterol was associated with 35% (95% CI: 26-44%) increased risk of coronary death, 25% (95% CI: 13-40%) increased risk of fatal or non-fatal ischaemic stroke, and 20% (95% CI: 8-30%) decreased risk of fatal haemorrhagic stroke. CONCLUSIONS: In both Asian and non-Asian populations in the Asia-Pacific region, total cholesterol is similarly strongly associated with the risk of CHD and ischaemic, but not haemorrhagic, stroke. Rising population-wide levels of cholesterol would be expected to contribute to a substantial increase in the overall burden of cardiovascular diseases in this region.

Adult↗

A comparison of the associations between risk factors and cardiovascular disease in Asia and Australasia.

BACKGROUND: Cardiovascular disease is already the leading cause of death in many Asian populations. Relationships between vascular risk factors and cardiovascular disease may differ in Asian and western populations. Previously, a lack of prospective data has prevented the reliable quantification of such differences, which, if they were shown to exist, would suggest that novel cardiovascular prevention and treatment strategies are required for Asia. DESIGN: An individual participant data meta-analysis of 32 studies from the Asia-Pacific region involving 331 100 subjects (75% from Asia; 25% from the predominantly Caucasian populations of Australia and New Zealand). METHODS: Outcomes were death from coronary heart disease, ischaemic and haemorrhagic stroke. Hazard ratios were estimated from Cox models for systolic blood pressure (SBP), total cholesterol, triglycerides, body mass index, diabetes and current cigarette smoking, stratified by study and sex and adjusted for age, the other risk factors and regression dilution. RESULTS: After an average period of follow-up of 4 years there were 2082 deaths from coronary heart disease, 600 from haemorrhagic stroke and 420 from ischaemic stroke. The direction and strength of the associations between risk factors and cardiovascular outcomes were similar in the two regions, although in two cases there were significant differences. Triglycerides were more strongly associated with coronary heart disease in Australia and New Zealand (P = 0.03), whereas SBP showed a stronger relationship with haemorrhagic stroke in Asia (P = 0.04). CONCLUSIONS: Classical vascular risk factors act similarly in Asian and Caucasian populations; prevention and treatment strategies should thus be similar. Blood pressure reduction should be particularly effective in Asia.

Asia↗

Global Initiative for Chronic Obstructive Lung Disease strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease: an Asia-Pacific perspective.

Chronic obstructive pulmonary disease (COPD) is a major public health problem and its prevalence and mortality are increasing throughout the world, including the Asia-Pacific region. To arrest these worldwide trends, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Expert Panel's global strategy for the diagnosis, management, and prevention of COPD was published in 2001. Based on recently published clinical trials, the GOLD statement was updated in 2003. The Asia-Pacific COPD Roundtable Group, a taskforce of expert respirologists from the Asia-Pacific region, has recently formulated a consensus statement on implementation of the GOLD strategy for COPD in the Asia-Pacific region. The key issues identified by the COPD Roundtable Group for comment are: (i) where there is no access to spirometry, diagnosis of COPD could be suspected on the basis of history, symptoms and physical signs; (ii) inhaled bronchodilators are the preferred regular treatment for COPD in the region, but oral bronchodilators may be considered if the cost of inhaled bronchodilators is a barrier to treatment; (iii) the use of a Metered Dose Inhaler with spacer in place of a nebulizer is recommended in the treatment of acute airflow obstruction in patients with COPD; (iv) influenza vaccination is recommended for all patients with COPD in communities where there is a high likelihood of Severe Acute Respiratory Syndrome; and (v) simplified pulmonary rehabilitation programmes should be established in areas where comprehensive programmes are unavailable. Physical exercise training and education on smoking cessation should be core elements of any rehabilitation program. In summary, the COPD Roundtable Group supports implementation of the GOLD strategy for the diagnosis, management and prevention of COPD in the Asia-Pacific region, subject to the additions and modifications to the guidelines suggested above.

Asia↗