Stephen Leeder

Priority actions for the non-communicable disease crisis

The UN High-Level Meeting on Non-Communicable Diseases (NCDs) in September, 2011, is an unprecedented opportunity to create a sustained global movement against premature death and preventable morbidity and disability from NCDs, mainly heart disease, stroke, cancer, diabetes, and chronic respiratory disease. The increasing global crisis in NCDs is a barrier to development goals including poverty reduction, health equity, economic stability, and human security. The Lancet NCD Action Group and the NCD Alliance propose five overarching priority actions for the response to the crisis--leadership, prevention, treatment, international cooperation, and monitoring and accountability--and the delivery of five priority interventions--tobacco control, salt reduction, improved diets and physical activity, reduction in hazardous alcohol intake, and essential drugs and technologies. The priority interventions were chosen for their health effects, cost-effectiveness, low costs of implementation, and political and financial feasibility. The most urgent and immediate priority is tobacco control. We propose as a goal for 2040, a world essentially free from tobacco where less than 5% of people use tobacco. Implementation of the priority interventions, at an estimated global commitment of about US

Preventing chronic diseases: how many lives can we save?

9 billion per year, will bring enormous benefits to social and economic development and to the health sector. If widely adopted, these interventions will achieve the global goal of reducing NCD death rates by 2% per year, averting tens of millions of premature deaths in this decade.

Changing prevalence of asthma in Australian children.

35 million people will die in 2005 from heart disease, stroke, cancer, and other chronic diseases. Only 20% of these deaths will be in high-income countries--while 80% will occur in low-income and middle-income countries. The death rates from these potentially preventable diseases are higher in low-income and middle-income countries than in high-income countries, especially among adults aged 30-69 years. The impact on men and women is similar. We propose a new goal for reducing deaths from chronic disease to focus prevention and control efforts among those concerned about international health. This goal-to reduce chronic disease death rates by an additional 2% annually--would avert 36 million deaths by 2015. An additional benefit will be a gain of about 500 million years of life over the 10 years from 2006 to 2015. Most of these averted deaths and life-years gained will be in low-income and middle-income countries, and just under half will be in people younger than 70 years. We base the global goal on worldwide projections of deaths by cause for 2005 and 2015. The data are presented for the world, selected countries, and World Bank income groups.

Importance of house dust mite and Alternaria allergens in childhood asthma: an epidemiological study in two climatic regions of Australia

Abstract Objective : To investigate whether prevalence of asthma in children increased in 10 years. Design : Serial cross sectional studies of two populations of children by means of standard protocol. Setting : Two towns in New South Wales: Belmont (coastal and humid) and Wagga Wagga (inland and dry). Subjects : Children aged 8-10 years: 718 in Belmont and 769 in Wagga Wagga in 1982; 873 in Belmont and 795 in Wagga Wagga in 1992. Main outcome measures : History of respiratory illness recorded by parents in self administered questionnaire; airway hyperresponsiveness by histamine inhalation test; atopy by skin prick tests; counts of house dust mites in domestic dust. Results : Prevalence of wheeze in previous 12 months increased in Belmont, from 10.4% (75/718) in 1982 to 27.6% (240/873) in 1992 (P<0.001), and in Wagga Wagga, from 15.5% (119/769) to 23.1% (183/795) (P<0.001). The prevalence of airway hyperresponsiveness increased twofold in Belmont to 19.8% (173/873) (P<0.001) and 1.4-fold in Wagga Wagga to 18.1% (P<0.05). The prevalence of airway hyperresponsiveness increased mainly in atopic children only, but the prevalence of atopy was unchanged (about 28.5% in Belmont and about 32.5% in Wagga Wagga). Numbers of house dust mites increased 5.5-fold in Belmont and 4.5-fold in Wagga Wagga. Conclusions : We suggest that exposure to higher allergen levels has increased airway abnormalities in atopic children or that mechanisms that protected airways of earlier generations of children have been altered by new environmental fators.

Identification of IL6R and chromosome 11q13.5 as risk loci for asthma

The relation of house dust mite allergen levels to asthma and allergy was examined in two population samples of children aged 8–11 years in northern New South Wales. We studied 805 children in Lismore (a hot, humid, coastal region) and 770 in Moree/ Narrabri (a hot, dry inland region). Respiratory symptoms were measured by questionnaire, bronchial hyperresponsiveness (BHR) by histamine inhalation test, and allergy by skin‐prick tests. Current asthma was defined as the presence of both wheeze in last 12 months and BHR. Der p I levels were measured in dust from the bed and floors in the homes of 57 randomly selected children in the coastal region and of 74 inland children. Der p I levels were significantly higher by the coast (83.0 vs 11.2 μg/g, P < 0.001). House dust mite sensitivity was of similar prevalence in both regions (28.6 vs 26.4%, n.s.) but Alternaria sensitivity was higher inland (4.0 vs 15.2%P < 0.001). Bronchial responsiveness was more severe in coastal children sensitized to house dust mites and in inland children who were sensitized to Alternaria. The adjusted odds ratios for current asthma in children sensitized to house dust mites were 21.3 (95% CI 10.5, 43.2) by the coast and 2.7 (95% CI 1.3, 5.4) inland, and in children sensitized to Alternaria were 3.4 (95% CI 1.3, 9.1) in the coastal region and 5.6 (95% CI 3.1, 10.1 inland. These studies suggest that high house dust mite allergen levels in a humid, subtropical region act to significantly increase bronchial responsiveness in sensitized children, and that Alternaria allergens have a similar but less potent action in a dry, rural region.

Asthma in preschool children: prevalence and risk factors

BACKGROUND We aimed to identify novel genetic variants affecting asthma risk, since these might provide novel insights into molecular mechanisms underlying the disease. METHODS We did a genome-wide association study (GWAS) in 2669 physician-diagnosed asthmatics and 4528 controls from Australia. Seven loci were prioritised for replication after combining our results with those from the GABRIEL consortium (n=26,475), and these were tested in an additional 25,358 independent samples from four in-silico cohorts. Quantitative multi-marker scores of genetic load were constructed on the basis of results from the GABRIEL study and tested for association with asthma in our Australian GWAS dataset. FINDINGS Two loci were confirmed to associate with asthma risk in the replication cohorts and reached genome-wide significance in the combined analysis of all available studies (n=57,800): rs4129267 (OR 1·09, combined p=2·4×10(-8)) in the interleukin-6 receptor (IL6R) gene and rs7130588 (OR 1·09, p=1·8×10(-8)) on chromosome 11q13.5 near the leucine-rich repeat containing 32 gene (LRRC32, also known as GARP). The 11q13.5 locus was significantly associated with atopic status among asthmatics (OR 1·33, p=7×10(-4)), suggesting that it is a risk factor for allergic but not non-allergic asthma. Multi-marker association results are consistent with a highly polygenic contribution to asthma risk, including loci with weak effects that might be shared with other immune-related diseases, such as NDFIP1, HLA-B, LPP, and BACH2. INTERPRETATION The IL6R association further supports the hypothesis that cytokine signalling dysregulation affects asthma risk, and raises the possibility that an IL6R antagonist (tocilizumab) may be effective to treat the disease, perhaps in a genotype-dependent manner. Results for the 11q13.5 locus suggest that it directly increases the risk of allergic sensitisation which, in turn, increases the risk of subsequent development of asthma. Larger or more functionally focused studies are needed to characterise the many loci with modest effects that remain to be identified for asthma. FUNDING National Health and Medical Research Council of Australia. A full list of funding sources is provided in the webappendix.

Retinal Arteriolar Narrowing Is Associated With 5-Year Incident Severe Hypertension The Blue Mountains Eye Study

BACKGROUND The prevalence of asthma in children has increased in many countries over recent years. To plan effective interventions to reverse this trend we need a better understanding of the risk factors for asthma in early life. This study was undertaken to measure the prevalence of, and risk factors for, asthma in preschool children. METHODS Parents of children aged 3–5 years living in two cities (Lismore, n=383; Wagga Wagga, n=591) in New South Wales, Australia were surveyed by questionnaire to ascertain the presence of asthma and various proposed risk factors for asthma in their children. Recent asthma was defined as ever having been diagnosed with asthma andhaving cough or wheeze in the last 12 monthsand having used an asthma medication in the last 12 months. Atopy was measured by skin prick tests to six common allergens. RESULTS The prevalence of recent asthma was 22% in Lismore and 18% in Wagga Wagga. Factors which increased the risk of recent asthma were: atopy (odds ratio (OR) 2.35, 95% CI 1.49 to 3.72), having a parent with a history of asthma (OR 2.05, 95% CI 1.34 to 3.16), having had a serious respiratory infection in the first 2 years of life (OR 1.93, 95% CI 1.25 to 2.99), and a high dietary intake of polyunsaturated fats (OR 2.03, 95% CI 1.15 to 3.60). Breast feeding (OR 0.41, 95% CI 0.22 to 0.74) and having three or more older siblings (OR 0.16, 95% CI 0.04 to 0.71) decreased the risk of recent asthma. CONCLUSIONS Of the factors tested, those that have the greatest potential to be modified to reduce the risk of asthma are breast feeding and consumption of polyunsaturated fats.

The effect of fiscal policy on diet, obesity and chronic disease: a systematic review

We assessed whether retinal arteriolar narrowing and structural abnormalities independently predicted 5-year incident severe (grade 2 or 3) hypertension in an older population-based cohort. The Blue Mountains Eye Study baseline (1992 to 1994) examined 3654 residents aged 49 and older in 2 postal code areas, west of Sydney. Of the 2335 participants (75.1% of survivors) who returned at the 5-year examinations, 1319 were normotensive or had mild (grade 1) hypertension at baseline. Baseline retinal photographs were graded for focal retinal vessel wall signs and vessel diameters were measured. Participants were classified as having normal, high-normal blood pressure [BP] (systolic BP 121 to 139 mm Hg and/or diastolic BP 81 to 89 mm Hg), mild hypertension (systolic BP 140 to 159 mm Hg and/or diastolic BP 90 to 99 mm Hg), or severe hypertension if they had a previous diagnosis of hypertension and were receiving antihypertensive medications or had systolic BP ≥160 mm Hg and/or diastolic BP ≥100 mm Hg at examination. Incident severe hypertension was defined in persons who were free of severe hypertension at baseline but classified as having severe hypertension at the 5-year examinations. Of the 1319 baseline subjects at risk, 390 (29.6%) developed severe hypertension. After adjusting for age, sex, body mass index, smoking, glucose, and total cholesterol, generalized retinal arteriolar narrowing at baseline was associated with increased risk of incident severe hypertension (odds ratio 2.6; 95% confidence interval, 1.7 to 3.9) when comparing the narrowest versus widest quintile. This association remained significant after further adjustment for baseline mean arterial BP or BP status. Our findings support the hypothesis that small vessel structural changes may precede the development of severe hypertension.

Retinal microvascular signs and risk of stroke and stroke mortality

OBJECTIVE To assess the effect of food taxes and subsidies on diet, body weight and health through a systematic review of the literature. METHODS We searched the English-language published and grey literature for empirical and modelling studies on the effects of monetary subsidies or taxes levied on specific food products on consumption habits, body weight and chronic conditions. Empirical studies were dealing with an actual tax, while modelling studies predicted outcomes based on a hypothetical tax or subsidy. FINDINGS Twenty-four studies met the inclusion criteria: 13 were from the peer-reviewed literature and 11 were published on line. There were 8 empirical and 16 modelling studies. Nine studies assessed the impact of taxes on food consumption only, 5 on consumption and body weight, 4 on consumption and disease and 6 on body weight only. In general, taxes and subsidies influenced consumption in the desired direction, with larger taxes being associated with more significant changes in consumption, body weight and disease incidence. However, studies that focused on a single target food or nutrient may have overestimated the impact of taxes by failing to take into account shifts in consumption to other foods. The quality of the evidence was generally low. Almost all studies were conducted in high-income countries. CONCLUSION Food taxes and subsidies have the potential to contribute to healthy consumption patterns at the population level. However, current evidence is generally of low quality and the empirical evaluation of existing taxes is a research priority, along with research into the effectiveness and differential impact of food taxes in developing countries.

Influence of family factors on the incidence of lower respiratory illness during the first year of life.

Objective: The purpose of this study was to assess the relation of retinal microvascular signs and incident stroke and stroke mortality in an older population. Methods: The authors took retinal photographs on baseline participants (3,654 patients aged 49+ years) of the Blue Mountains Eye Study (1992 to 1994). They assessed the presence of retinopathy (microaneurysms, retinal hemorrhages) in participants without diabetes and retinal arteriolar signs in all participants using standardized grading protocols. Incident stroke/TIA/cerebrovascular death (combined stroke events) were identified at follow-up examinations during 1997 to 1999. Results: During a 7-year period, 859 participants died, 97 (11.3%) of which died of cerebrovascular causes. Of survivors, 24 had confirmed incident stroke, and 11 had incident TIA. Combined stroke events were more frequent in participants with retinopathy (5.7%), with moderate/severe arteriovenous nicking (4.2%), or with focal arteriolar narrowing (7.2%) compared with those without (1.9%). After controlling for age, sex, systolic blood pressure, smoking, and self-rated health, retinopathy was significantly associated with combined stroke events (relative risk [RR] 1.7, 95% CI 1.0 to 2.8) in persons without diabetes. This association was stronger in those without severe hypertension (RR 2.7, CI 1.2 to 6.2) or in persons with two or more retinal microvascular signs (RR 2.7, CI 1.5 to 5.2). Generalized or focal arteriolar narrowing or arteriovenous nicking was not independently associated with combined stroke events after multivariate adjustment. Conclusions: In older Australians without diabetes, retinopathy signs predict stroke or stroke-related death independent of traditional stroke risk factors.