Estimates of global mortality attributable to smoking in 2000

Background Smoking is a risk factor for several diseases and has been increasing in many developing countries. Our aim was to estimate global and regional mortality in 2000 caused by smoking, including an analysis of uncertainty. Methods Following the methods of Peto and colleagues, we used lung-cancer mortality as an indirect marker for accumulated smoking risk. Never-smoker lung-cancer mortality was estimated based on the household use of coal with poor ventilation. Relative risks were taken from the American Cancer Society Cancer Prevention Study, phase II, and the retrospective proportional mortality analysis of Liu and colleagues in China. Relative risks were corrected for confounding and extrapolation to other regions. Results We estimated that in 2000, 4.83 (uncertainty range 3.94-5.93) million premature deaths in the world were attributable to smoking; 2.41 (1.80-3.15) million in developing countries and 2.43 (2.13-2.78) million in industrialised countries. 3.84 million of these deaths were in men. The leading causes of death from smoking were cardiovascular diseases (1.69 million deaths), chronic obstructive pulmonary disease (0.97 million deaths), and lung cancer (0.85 million deaths). Interpretation Smoking was an important cause of global mortality in 2000. In view of the expected demographic and epidemiological transitions and current smoking patterns in the developing world, the health loss due to smoking will grow even larger unless effective interventions and policies that reduce smoking among men and prevent increases among women in developing countries are implemented.

Mannose-binding lectin gene polymorphism predicts hospital admissions for COPD infections

Infection frequently causes exacerbations of chronic obstructive pulmonary disease (COPD). Mannose-binding lectin (MBL) is a pattern-recognition receptor that assists in clearing microorganisms. Polymorphisms in the MBL2 gene reduce serum MBL levels and are associated with risk of infection. We studied whether the MBL2 codon 54 B allele affected serum MBL levels, admissions for infective exacerbation in COPD and disease susceptibility. Polymorphism frequency was determined by PCR-RFLP in 200 COPD patients and 104 smokers with normal lung function. Serum MBL was measured as mannan-binding activity in a subgroup of 82 stable COPD patients. Frequency of COPD admissions for infective exacerbation was ascertained for a 2-year period. The MBL2 codon 54 B allele reduced serum MBL in COPD patients. In keeping, patients carrying the low MBL-producing B allele had increased risk of admission for infective exacerbation (OR 4.9, P-corrected = 0.011). No association of MBL2 genotype with susceptibility to COPD was detected. In COPD, serum MBL is regulated by polymorphism at codon 54 in its encoding gene. Low MBL-producing genotypes were associated with more frequent admissions to hospital with respiratory infection, suggesting that the MBL2 gene is disease-modifying in COPD. MBL2 genotype should be explored prospectively as a prognostic marker for infection risk in COPD.

Estimates of global and regional potential health gains from reducing multiple major risk factors

Background Estimates of the disease burden due to multiple risk factors can show the potential gain from combined preventive measures. But few such investigations have been attempted, and none on a global scale. Our aim was to estimate the potential health benefits from removal of multiple major risk factors. Methods We assessed the burden of disease and injury attributable to the joint effects of 20 selected leading risk factors in 14 epidemiological subregions of the world. We estimated population attributable fractions, defined as the proportional reduction in disease or mortality that would occur if exposure to a risk factor were reduced to an alternative level, from data for risk factor prevalence and hazard size. For every disease, we estimated joint population attributable fractions, for multiple risk factors, by age and sex, from the direct contributions of individual risk factors. To obtain the direct hazards, we reviewed publications and re-analysed cohort data to account for that part of hazard that is mediated through other risks. Results Globally, an estimated 47% of premature deaths and 39% of total disease burden in 2000 resulted from the joint effects of the risk factors considered. These risks caused a substantial proportion of important diseases, including diarrhoea (92%-94%), lower respiratory infections (55-62%), lung cancer (72%), chronic obstructive pulmonary disease (60%), ischaemic heart disease (83-89%), and stroke (70-76%). Removal of these risks would have increased global healthy life expectancy by 9.3 years (17%) ranging from 4.4 years (6%) in the developed countries of the western Pacific to 16.1 years (43%) in parts of sub-Saharan Africa. Interpretation Removal of major risk factors would not only increase healthy life expectancy in every region, but also reduce some of the differences between regions, The potential for disease prevention and health gain from tackling major known risks simultaneously would be substantial.

Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data

Background Our aim was to calculate the global burden of disease and risk factors for 2001, to examine regional trends from 1990 to 2001, and to provide a starting point for the analysis of the Disease Control Priorities Project (DCPP). Methods We calculated mortality, incidence, prevalence, and disability adjusted life years (DALYs) for 136 diseases and injuries, for seven income/geographic country groups. To assess trends, we re-estimated all-cause mortality for 1990 with the same methods as for 2001. We estimated mortality and disease burden attributable to 19 risk factors. Findings About 56 million people died in 2001. Of these, 10.6 million were children, 99% of whom lived in low-and-middle-income countries. More than half of child deaths in 2001 were attributable to acute respiratory infections, measles, diarrhoea, malaria, and HIV/AIDS. The ten leading diseases for global disease burden were perinatal conditions, lower respiratory infections, ischaemic heart disease, cerebrovascular disease, HIV/AIDS, diarrhoeal diseases, unipolar major depression, malaria, chronic obstructive pulmonary disease, and tuberculosis. There was a 20% reduction in global disease burden per head due to communicable, maternal, perinatal, and nutritional conditions between 1990 and 2001. Almost half the disease burden in low-and-middle-income countries is now from non-communicable diseases (disease burden per head in Sub-Saharan Africa and the low-and-middle-income countries of Europe and Central Asia increased between 1990 and 2001). Undernutrition remains the leading risk factor for health loss. An estimated 45% of global mortality and 36% of global disease burden are attributable to the joint hazardous effects of the 19 risk factors studied. Uncertainty in all-cause mortality estimates ranged from around 1% in high-income countries to 15-20% in Sub-Saharan Africa. Uncertainty was larger for mortality from specific diseases, and for incidence and prevalence of non-fatal outcomes. Interpretation Despite uncertainties about mortality and burden of disease estimates, our findings suggest that substantial gains in health have been achieved in most populations, countered by the HIV/AIDS epidemic in Sub-Saharan Africa and setbacks in adult mortality in countries of the former Soviet Union. our results on major disease, injury, and risk factor causes of loss of health, together with information on the cost-effectiveness of interventions, can assist in accelerating progress towards better health and reducing the persistent differentials in health between poor and rich countries.

Prolonged effects of a home-based intervention in patients with chronic illness

Background: Data on the long-term benefits of nonspecific disease management programs are limited. We performed a long-term follow-up of a previously published randomized trial. Methods: We compared all-cause mortality and recurrent hospitalization during median follow-up of 7.5 years in a heterogeneous cohort of patients with chronic illness initially exposed to a multidisciplinary, homebased intervention (HBI) (n = 260) or to usual postdischarge care (n = 268). Results: During follow-up, HBI had no impact on all-cause mortality (relative risk, 1.04; 95% confidence interval, 0.80-1.35) or event-free survival from death or unplanned hospitalization (relative risk, 1.03; 95% confidence interval, 0.86-1.24). Initial analysis suggested that HBI had only a marginal impact in reducing unplanned hospitalization, with 677 readmissions vs 824 for the usual care group (mean +/- SD rate, 0.72 +/- 0.96 vs 0.84 +/- 1.20 readmissions/patient per year; P = .08). When accounting for increased hospital activity in HBI patients with chronic obstructive pulmonary disease during follow-up for 2 years, post hoc analyses showed that HBI reduced readmissions by 14% within 2 years in patients without this condition (mean +/- SD rate, 0.54 +/- 0.72 vs 0.63 +/- 0.88 readmission/patient per year; P =. 04) and by 21% in all surviving patients within 3 to 8 years (mean +/- SD rate, 0.64 +/- 1.26 vs 0.81 +/- 1.61 readmissions/ patient per year; P =. 03). Overall, recurrent hospital costs were significantly lower ( 14%) in the HBI group (mean +/- SD, $ 823 +/- $ 1642 vs $ 960 +/- $ 1376 per patient per year; P =. 045). Conclusion: This unique study suggests that a nonspecific HBI provides long-term cost benefits in a range of chronic illnesses, except for chronic obstructive pulmonary disease.

Drug use evaluation of ipratropium bromide at two tertiary referral hospitals in Brisbane.

Objective: To assess the appropriateness of ipratropium bromide prescribing in two tertiary referral hospitals. Method: Criteria for optimal use were developed based on current literature and modified after consultation with respiratory physicians and clinical pharmacists. A prospective review of prescribing was performed over a 2-month period to assess conformity to these criteria. Results: Information was collected from 84 patients; 5% were receiving inhalers and 96% nebuliser therapy (one patient used both). 77% of patients (n = 65) had a principal diagnosis of chronic obstructive pulmonary disease, 14% (n = 12) asthma and 8% (n = 7) had neither diagnosis. 75% of patients were using ipratropium outside the guidelines. The major areas where the guidelines were not met were a lack of therapeutic justification, use of inappropriate doses, and use of an inappropriate delivery device. Feedback and educational interventions were designed and delivered based on the data obtained. Conclusions: There was widespread use of ipratropium outside the developed guidelines. Interventions in specific areas could lead to significant improvements in the use of this high cost drug

Coal dust exposures in the longwall mines of New South Wales, Australia: a respiratory risk assessment

This paper presents an analysis of personal respirable coal dust measurements recorded by the Joint Coal Board in the underground longwall mines of New South Wales from 1985 to 1999. A description of the longwall mining process is given. In the study, 11 829 measurements from 33 mines were analysed and the results given for each occupation, for seven occupational groups, for individual de-identified mines and for each year of study. The mean respirable coal dust concentration for all jobs was 1.51 mg/m(3) (SD 1.08 mg/m(3)). Only 6.9% of the measurements exceeded the Australian exposure standard of 3 mg/m(3). Published exposure-response relationships were used to predict the prevalence of progressive massive fibrosis and the mean loss of FEV1, after a working lifetime (40 years) of exposure to the mean observed concentration of 1.5 mg/m(3). Prevalences of 1.3 and 2.9% were predicted, based on data from the UK and the USA, respectively. The mean loss of FEV1 was estimated to be 73.7 ml.

Focusing in on structural genomics: The University of Queensland structural biology pipeline

The flood of new genomic sequence information together with technological innovations in protein structure determination have led to worldwide structural genomics (SG) initiatives. The goals of SG initiatives are to accelerate the process of protein structure determination, to fill in protein fold space and to provide information about the function of uncharacterized proteins. In the long-term, these outcomes are likely to impact on medical biotechnology and drug discovery, leading to a better understanding of disease as well as the development of new therapeutics. Here we describe the high throughput pipeline established at the University of Queensland in Australia. In this focused pipeline, the targets for structure determination are proteins that are expressed in mouse macrophage cells and that are inferred to have a role in innate immunity. The aim is to characterize the molecular structure and the biochemical and cellular function of these targets by using a parallel processing pipeline. The pipeline is designed to work with tens to hundreds of target gene products and comprises target selection, cloning, expression, purification, crystallization and structure determination. The structures from this pipeline will provide insights into the function of previously uncharacterized macrophage proteins and could lead to the validation of new drug targets for chronic obstructive pulmonary disease and arthritis. (c) 2006 Elsevier B.V. All rights reserved.

The effect of tidal volume and peep on CO2 and oxygenation during resuscitation of very premature lambs

Background: Over-ventilation causing low arterial carbon dioxide levels (PaCO2) has been associated with the development of neonatal chronic lung disease and adverse outcomes. This may occur very soon after birth. Aim: To investigate the effect on PaCO2 and oxygenation of very premature lambs resuscitated with different tidal volumes and PEEP. Methods: Anaesthetised lambs delivered at 126 days gestation were randomised to 15 min resuscitation with 3 regimes: (1) Laerdal resuscitation bag (B) with 100% oxygen and no PEEP, (2) fixed tidal volume (VT) of 5 mL/kg, or (3) VT of 10 mL/kg, both delivered with a Babylog 8000 ventilator in volume guarantee mode with 8 cm H2O PEEP and variable FiO2. Frequent blood gases were measured and VT, mean airway pressure (Paw), minute volume (MV), ventilation rate (VR), respiratory system compliance (Crs) and alveolar/arterial oxygen difference (AaDO2) were recorded. Results: Twenty lambs were studied. B (1) was associated with more variable VT and peak inspiratory pressures (PIP) compared to fixed tidal volumes (2 and 3). The lambs ventilated with 10 mL/kg were over-ventilated, those ventilated with 5 mL/kg were slightly under-ventilated. Those ventilated with the Laerdal bag had a mean VT of 7.5 mL/kg and were normocarbic. The different tidal volumes had little effect on oxygenation. PEEP improved oxygenation. The table shows the values at 15 minutes expressed as mean and SEM. TABLE. No caption av... TABLE. No caption av... Image Tools Conclusion: Very premature lambs can be effectively resuscitated from birth using volume guarantee ventilation. Within minutes of birth different tidal volumes had a large effect on PaCO2 and no effect on oxygenation. Studies are needed to determine the appropriate tidal volume for resuscitating very premature infants to maintain acceptable levels of PaCO2. © International Pediatrics Research Foundation, Inc. 2004. All Rights Reserved.

Gene complementation of airway epithelium in the cystic fibrosis mouse is necessary and sufficient to correct the pathogen clearance and inflammatory abnormalities

Increasingly, cystic fibrosis (CF) is regarded as an inflammatory disorder where the response of the lung to Pseudomonas aeruginosa is exaggerated as a consequence of processes mediated by the product of the CF gene, CFTR. Of importance to any gene-replacement strategy for treatment of CF is the identification of the cell type(s) within the lung milieu that need to be corrected and an indication whether this is sufficient to restore a normal inflammatory response and bacterial clearance. We generated G551D CF mice transgenically expressing the human CFTR gene in two tissue compartments previously demonstrated to mediate a CFTR-dependent inflammatory response: lung epithelium and alveolar macrophages. Following chronic pulmonary infection with P. aeruginosa, CF mice with epithelial-expressed but not macrophage-specific CFTR showed an improvement in pathogen clearance and inflammatory markers compared with control CF animals. Additionally, these data indicate the general role for epithelial cell-mediated events in the response of the lung to bacterial pathogens and the importance of CFTR in mediating these processes.

Respiratory health effects of cannabis: Position statement of the Thoracic Society of Australia and New Zealand

Both the gaseous and the particulate phases of tobacco and cannabis smoke contain a similar range of harmful chemicals. However, differing patterns of inhalation mean that smoking a 'joint' of cannabis results in exposure to significantly greater amounts of combusted material than with a tobacco cigarette. The histopathological effects of cannabis smoke exposure include changes consistent with acute and chronic bronchitis. Cellular dysplasia has also been observed, suggesting that, like tobacco smoke, cannabis exposure has the potential to cause malignancy. These features are consistent with the clinical presentation. Symptoms of cough and early morning sputum production are common (20-25%) even in young individuals who smoke cannabis alone. Almost all studies indicate that the effects of cannabis and tobacco smoking are additive and independent. Public health education should dispel the myth that cannabis smoking is relatively safe by highlighting that the adverse respiratory effects of smoking cannabis are similar to those of smoking tobacco, even although it remains to be confirmed that smoking cannabis alone leads to the development of chronic lung disease.

Psychoeducational outcome at school age of preterm infants with bronchopulmonary dysplasia

Objective: To investigate the cognitive performance and educational attainment at school-age of children with bronchopulmonary dysplasia (BPD), compared with a preterm control group of children. Methods: Seventy preterm infants with BPD and 61 birth weight matched controls were prospectively followed-up to school-age. The Weschler Intelligence Scale for Children - III (WISC), the Wide Range Achievement Test (WRAT) and the Developmental Test of Visual Motor Integration (VMI) were administered. The results were compared between the two groups and multiple regression analyses were performed to determine the effect of confounding variables. Results: The children in the BPD group performed less well on the Full Scale IQ (mean 86.7 vs 93.5; 95% CI, 1.9-11.7), Verbal IQ (mean 87.1 vs 94.1; 95% CI, 2.0-12.0) and the Performance IQ (mean 88.6 vs 95.2; 95% CI, 2.0-11.2) of the WISC, the reading component of the WRAT (mean 93.8 vs 98.9; 95% CI, 0.3-9.8) and the VMI (mean 88.9 vs 93.3; 95%, CI 1.1-7.8). Despite controlling for social and biological variables, statistical differences persisted for Full Scale and Verbal IQ and reading. A Verbal IQ >1 SD below the mean was found in 41% of BPD children compared to 21% of controls, while on the reading component of the WRAT a greater proportion of BPD children also had scores>1 SD below the mean. Conclusion: Impaired psychoeducational performance was found in preterm children with BPD compared to controls, especially in the areas of language abilities and reading skills. This supports a greater need for special educational services and counseling for parents for these children.