Multilevel regression modelling to investigate variation in disease prevalence across locations

In this article, we show how to investigate the role of individual (personal) risk factors in outcome prevalence in multicentre studies with multilevel modelling. The variation in outcome prevalence is modelled by introducing a random intercept. In the next step, the empty model is compared with the model containing the risk factor(s). Because the outcome is dichotomous, this comparison can only be carried out after having rescaled the models’ parameter values to the variance of an underlying continuous variable. We illustrate this approach with data from Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC) and provide a corresponding Stata do-file

Overweight/Obesity and Respiratory and Allergic Disease in Children: International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two

BackgroundChildhood obesity and asthma are increasing worldwide. A possible link between the two conditions has been postulated.MethodsCross-sectional studies of stratified random samples of 8–12-year-old children (n = 10 652) (16 centres in affluent and 8 centres in non-affluent countries) used the standardized methodology of ISAAC Phase Two. Respiratory and allergic symptoms were ascertained by parental questionnaires. Tests for allergic disease were performed. Height and weight were measured, and overweight and obesity were defined according to international definitions. Prevalence rates and prevalence odds ratios were calculated.ResultsOverweight (odds ratio = 1.14, 95%-confidence interval: 0.98; 1.33) and obesity (odds ratio = 1.67, 95%-confidence interval: 1.25; 2.21) were related to wheeze. The relationship was stronger in affluent than in non-affluent centres. Similar results were found for cough and phlegm, rhinitis and eczema but the associations were mostly driven by children with wheeze. There was a clear association of overweight and obesity with airways obstruction (change in FEV1/FVC, −0.90, 95%-confidence interval: −1.33%; −0.47%, for overweight and −2.46%, 95%-confidence interval: −3.84%; −1.07%, for obesity) whereas the results for the other objective markers, including atopy, were null.ConclusionsOur data from a large international child population confirm that there is a strong relation of body mass index with wheeze especially in affluent countries. Moreover, body mass index is associated with an objective marker of airways obstruction (FEV1/FVC) but no other objective markers of respiratory and allergic disorders

Barriers and enablers for integrating public health cobenefits in urban climate policy

Urban climate policy offers a significant opportunity to promote improved public health. The evidence around climate and health cobenefits is growing but has yet to translate into widespread integrated policies. This article presents two systematic reviews: first, looking at quantified cobenefits of urban climate policies, where transportation, land use, and buildings emerge as the most studied sectors; and second, looking at review papers exploring the barriers and enablers for integrating these health cobenefits into urban policies. The latter reveals wide agreement concerning the need to improve the evidence base for cobenefits and consensus about the need for greater political will and leadership on this issue. Systems thinking may offer a way forward to help embrace complexity and integrate health cobenefits into decision making. Knowledge coproduction to bring stakeholders together and advance policy-relevant research for urban health will also be required. Action is needed to bring these two important policy agendas together

Urban climate policy and action through a health lens-an untapped opportunity

Motivated by a growing recognition of the climate emergency, reflected in the 26th Conference of the Parties (COP26), we outline untapped opportunities to improve health through ambitious climate actions in cities. Health is a primary reason for climate action yet is rarely integrated in urban climate plans as a policy goal. This is a missed opportunity to create sustainable alliances across sectors and groups, to engage a broad set of stakeholders, and to develop structural health promotion. In this statement, we first briefly review the literature on health co-benefits of urban climate change strategies and make the case for health-promoting climate action; we then describe barriers to integrating health in climate action. We found that the evidence-base is often insufficiently policy-relevant to be impactful. Research rarely integrates the complexity of real-world systems, including multiple and dynamic impacts of strategies, and consideration of how decision-making processes contend with competing interests and short-term electoral cycles. Due to siloed-thinking and restrictive funding opportunities, research often falls short of the type of evidence that would be most useful for decision-making, and research outputs can be cryptic to decision makers. As a way forward, we urge researchers and stakeholders to engage in co-production and systems thinking approaches. Partnering across sectors and disciplines is urgently needed so pathways to climate change mitigation and adaptation fully embrace their health-promoting potential and engage society towards the huge transformations needed. This commentary is endorsed by the International Society for Environmental Epidemiology (ISEE) and the International Society for Urban Health (ISUH) and accompanies a sister statement oriented towards stakeholders (published on the societies’ websites)

Quantifying the health impacts of ambient air pollutants: recommendations of a WHO/Europe project.

OBJECTIVE: Quantitative estimates of air pollution health impacts have become an increasingly critical input to policy decisions. The WHO project "Health risks of air pollution in Europe--HRAPIE" was implemented to provide the evidence-based concentration-response functions for quantifying air pollution health impacts to support the 2013 revision of the air quality policy for the European Union (EU). METHODS: A group of experts convened by WHO Regional Office for Europe reviewed the accumulated primary research evidence together with some commissioned reviews and recommended concentration-response functions for air pollutant-health outcome pairs for which there was sufficient evidence for a causal association. RESULTS: The concentration-response functions link several indicators of mortality and morbidity with short- and long-term exposure to particulate matter, ozone and nitrogen dioxide. The project also provides guidance on the use of these functions and associated baseline health information in the cost-benefit analysis. CONCLUSIONS: The project results provide the scientific basis for formulating policy actions to improve air quality and thereby reduce the burden of disease associated with air pollution in Europe

Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies

Dissociation between skin test reactivity and anti-aeroallergen IgE: Determinants among urban Brazilian children.

BACKGROUND: The dissociation between specific IgE and skin prick test reactivity to aeroallergens, a common finding in populations living in low and middle-income countries, has important implications for the diagnosis and treatment of allergic diseases. Few studies have investigated the determinants of this dissociation. In the present study, we explored potential factors explaining this dissociation in children living in an urban area of Northeast Brazil, focusing in particular on factors associated with poor hygiene. METHODS: Of 1445 children from low income communities, investigated for risk factors of allergies, we studied 481 with specific IgE antibodies to any of Blomia tropicalis, Dermatophagoides pteronyssinus, Periplaneta americana and Blatella germanica allergens. Data on demographic, environmental and social exposures were collected by questionnaire; serum IgG and stool examinations were done to detect current or past infections with viral, bacterial, protozoan and intestinal helminth pathogens. We measured atopy by skin prick testing (SPT) and specific IgE (sIgE) to aerollergens in serum (by ImmunoCAP). SIgE reactivity to B. tropicalis extract depleted of carbohydrates was measured by an in-house ELISA. Total IgE was measured by in house capture ELISA. SNPs were typed using Illumina Omni 2.5. RESULTS: Negative skin prick tests in the presence of specific IgE antibodies were frequent. Factors independently associated with a reduced frequency of positive skin prick tests were large number of siblings, the presence of IgG to herpes simplex virus, Ascaris lumbricoides and Trichuris trichiura infections, living in neighborhoods with infrequent garbage collection, presence of rodents and cats in the household and sIgE reactivity to glycosylated B. tropicalis allergens. Also, SNP on IGHE (rs61737468) was negatively associated with SPT reactivity. CONCLUSIONS: A variety of factors were found to be associated with decreased frequency of SPT such as unhygienic living conditions, infections, total IgE, IgE response to glycosylated allergens and genetic polymorphisms, indicating that multiple mechanisms may be involved. Our data, showing that exposures to an unhygienic environment and childhood infections modulate immediate allergen skin test reactivity, provide support for the "hygiene hypothesis"

Long-term air pollution exposure and Parkinson's disease mortality in a large pooled European cohort: An ELAPSE study

BACKGROUND: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson's Disease (PD) remains limited. OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts. METHODS: Within the project 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (O3), as well as 8 PM2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders. RESULTS: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM2.5 (hazard ratio per 5 µg/m3: 1.25; 95% confidence interval: 1.01-1.55), NO2 (1.13; 0.95-1.34 per 10 µg/m3), and BC (1.12; 0.94-1.34 per 0.5 × 10-5m-1), and a negative association with O3 (0.74; 0.58-0.94 per 10 µg/m3). Associations of PM2.5, NO2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM2.5 remained robust when adjusted for NO2 (1.24; 0.95-1.62) or BC (1.28; 0.96-1.71), whereas associations with NO2 or BC attenuated to null. O3 associations remained negative, but no longer statistically significant in models with PM2.5. We detected suggestive positive associations with the potassium component of PM2.5. CONCLUSION: Long-term exposure to PM2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality