Asthma: a major pediatric health issue

The incidence, prevalence, and mortality of asthma have increased in children over the past three to four decades, although there has been some decline in the most recent decade. These trends are particularly marked and of greatest concern in preschool children. Internationally, there are huge variations among countries and continents, as demonstrated by the International Study of Asthma and Allergies in Childhood. In general, asthma rates were highest in English-speaking countries (UK, New Zealand, Australia, and North America) and some Latin American countries (Peru and Costa Rica), and lowest in South Korea, Russia, Uzbekistan, Indonesia, and Albania. There is currently no unifying hypothesis to explain these trends or any associated risk factors. Environmental factors that may lead to asthma include air pollution; genetic factors, the hygiene hypothesis, and lifestyle differences also play potentially causative roles. Asthma may develop as a result of persistent activation of the immune system alone or in combination with physiologic airway remodeling in early childhood. Further studies are needed to confirm this hypothesis.     

The microbiology of asthma

Asthma remains an important human disease that is responsible for substantial worldwide morbidity and mortality. The causes of asthma are multifactorial and include a complex mix of environmental, immunological and host genetic factors. In addition, epidemiological studies show strong associations between asthma and infection with respiratory pathogens, including common respiratory viruses such as rhinoviruses, human respiratory syncytial virus, adenoviruses, coronaviruses and influenza viruses, as well as bacteria (including atypical bacteria) and fungi. In this Review, we describe the many roles of microorganisms in the risk of developing asthma and in the pathogenesis of and protection against the disease, and we discuss the mechanisms by which infections affect the severity and prevalence of asthma.     

Air pollution and the lung: epidemiological approach

Epidemiological evidence has concurred with clinical and experimental evidence to correlate current levels of ambient air pollution, both indoors and outdoors, with respiratory effects. In this respect, the use of specific epidemiological methods has been crucial. Common outdoor pollutants are particulate matter, nitrogen dioxide, carbon monoxide, volatile organic compounds and ozone. Short-term effects of outdoor air pollution include changes in lung function, respiratory symptoms and mortality due to respiratory causes. Increase in the use of health care resources has also been associated with short-term effects of air pollution. Long-term effects of cumulated exposure to urban air pollution include lung growth impairment, chronic obstructive pulmonary disease (COPD), lung cancer, and probably the development of asthma and allergies. Lung cancer and COPD have been related to a shorter life expectancy. Common indoor pollutants are environmental tobacco smoke, particulate matter, nitrogen dioxide, carbon monoxide, volatile organic compounds and biological allergens. Concentrations of these pollutants can be many times higher indoors than outdoors. Indoor air pollution may increase the risk of irritation phenomena, allergic sensitisation, acute and chronic respiratory disorders and lung function impairment. Recent conservative estimates have shown that 1.5-2 million deaths per year worldwide could be attributed to indoor air pollution. Further epidemiological research is necessary to better evaluate the respiratory health effects of air pollution and to implement protective programmes for public health.     

Influence of adipose tissue immune dysfunction on childhood obesity

In recent decades, a dramatic rise has been observed in the prevalence of obesity in childhood and adolescence, along with an increase in fetal microsomia rates. The increased risk of obesity during this key period in development negatively affects the health of the individual later in life. Immune cells residing and recruited to white adipose tissue have been highlighted as important factors contributing to the pathogenesis of childhood obesity. Immune dysfunction in the context of obesity begins early in childhood, which is different from the pathological characteristics and influencing factors of adipose immunity in adults. Here, we explore the current understanding of the roles of childhood and early life events that result in high risks for obesity by influencing adipose tissue immune dysfunction under the pathological condition of obesity. Such knowledge will help in determining the mechanisms of childhood and early life obesity in efforts to ameliorate chronic inflammation-related metabolic diseases.     

Maternal high-fat diet programming of the neuroendocrine system and behavior

This article is part of a Special Issue “SBN 2014”.Maternal obesity, metabolic state, and diet during gestation have profound effects on offspring development. The prevalence of neurodevelopmental and mental health disorders has risen rapidly in the last several decades in parallel with the rise in obesity rates. Evidence from epidemiological studies indicates that maternal obesity and metabolic complications increase the risk of offspring developing behavioral disorders such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and schizophrenia. Animal models show that a maternal diet high in fat similarly disrupts behavioral programming of offspring, with animals showing social impairments, increased anxiety and depressive behaviors, reduced cognitive development, and hyperactivity. Maternal obesity, metabolic conditions, and high fat diet consumption increase maternal leptin, insulin, glucose, triglycerides, and inflammatory cytokines. This leads to increased risk of placental dysfunction, and altered fetal neuroendocrine development. Changes in brain development that likely contribute to the increased risk of behavioral and mental health disorders include increased inflammation in the brain, as well as alterations in the serotonergic system, dopaminergic system and hypothalamic–pituitary–adrenal (HPA) axis.     

West Sweden Asthma Study: Prevalence trends over the last 18 years argues no recent increase in asthma

Asthma prevalence has increased over the last fifty years, but the more recent changes have not been conclusively determined. Studies in children indicate that a plateau in the prevalence of asthma may have been reached, but this has not yet been confirmed in adults. Epidemiological studies have suggested that the prevalence of asthma in adults is approximately 7-10% in different parts of the western world.We have now performed a large-scale epidemiological evaluation of the prevalence of asthma and respiratory symptoms in adults between the ages of 16-75 in West Sweden. Thirty thousand randomly chosen individuals were sent a detailed questionnaire focusing on asthma and respiratory symptoms, as well possible risk factors. Sixty-two percent of the contacted individuals responded to the questionnaire. Asthma prevalence, defined as asthma diagnosed by a physician, was 8.3%. Moreover, the prevalence of respiratory symptoms was lower compared to previous studies. The most common respiratory symptom was any wheeze (16.6%) followed by sputum production (13.3%). In comparison with studies performed 18 years ago, the prevalence of asthma has not increased, and the prevalence of most respiratory symptoms has decreased. Therefore, our data argues that the continued increase in asthma prevalence that has been observed over the last half century is over.     

Childhood obesity and parental smoking as risk factors for childhood ADHD in Liverpool children

ADHD prevalence has risen in parallel with rising prevalence of pregnancy smoking and childhood obesity. The objective was to determine the epidemiological association of pregnancy smoking and childhood obesity with ADHD. A cross-sectional community study was conducted in 2006 using a parental questionnaire. A total of 1,074 schoolchildren aged 5-11 years were enrolled from 15 primary schools in a lower socio-economic area of Merseyside. ADHD was defined by the question "does your child have Attention Deficit Hyperactivity Disorder, (ADHD), which has been diagnosed by a doctor?" The prevalence estimates for childhood obesity, maternal smoking during pregnancy and childhood ADHD were 14.9% (116/777), 28.0% (269/955), and 3.4% (32/945), respectively. ADHD prevalence increased fivefold in children with obesity (RR, 4.80, 95% CI 2.2-10.4, P < 0.001) and more than twofold in children of mothers who smoked during pregnancy (RR, 2.44, 95% CI 1.2-4.9, P = 0.02). Regression analysis adjusting for obesity, overweight, maternal smoking during pregnancy, heavy maternal smoking, household member smoking during pregnancy, doctor-diagnosed asthma, preterm birth, and low birthweight showed significant independent associations of ADHD prevalence with obesity (AOR, 4.66, 95% CI 1.57-13.89, P = 0.006) and pregnancy smoking (AOR, 3.19, 95% CI 1.08-9.49, P = 0.04). There was a positive dose-response association of ADHD with the number of maternal cigarettes smoked during pregnancy. Measures to reduce both smoking among pregnant women and childhood obesity might reduce prevalence of childhood ADHD.     

Examining the temporal relationships between childhood obesity and asthma

Childhood obesity has become an issue of increasing concern to health researchers and policymakers in the United States. One important chronic health condition linked to obesity is pediatric asthma. Although researchers have speculated that both conditions may have common origins, the majority of research in this area has focused on a unidirectional relationship between obesity and later asthma. However, much of the literature is limited by its reliance on cross-sectional data and its failure to examine the possibility that asthma may influence weight fluctuations through changes in physical and sedentary activity. Using data from the Early Childhood Longitudinal Study-Kindergarten Cohort (ECLS-K), I explore the bidirectional relationships between childhood obesity and asthma. The results in this paper suggest that past asthma levels are positively correlated with changes in BMI and the onset of obesity. However, only new onset asthma is positively correlated with subsequent changes in BMI. The potential mechanisms are unclear, as I find little evidence that asthma is structurally related to changes in physical or sedentary activity over time. When testing the prevailing hypothesis that obesity is related to subsequent asthma, I find that lagged weight status is strongly related to asthma prevalence levels but that the onset of overweight or obesity is not associated with the subsequent onset of asthma. These results suggest that the onset of asthma may be related to subsequent weight gain over time.     

Letter: Trimethoprim-sulfamethoxazole: in vitro sensitivity of 1000 clinical isolates.

Certain “primitive” peoples such as traditional-living nomadic Eskimos have as yet been spared from the current epidemic of ischemic heart disease. A review of risk factors for underdeveloped populations suggests that environment rather than constitution is responsible. Favourable factors include the absence of overeating, a substantial level of of physical activity, only recent acquisition of the cigarette habit and absence of competitiveness. However, risk factors generally operate as in the “white” community, and where a Western lifestyle is embraced through either migration or acculturation the prevalence of ischemic heart disease rapidly increases to the levels encountered in “civilized” groups.     

Cardiac Health in Women With Metabolic Syndrome: Clinical Aspects and Pathophysiology

Although the classical cardiovascular risk factors (e.g., smoking and hypertension) are becoming more effectively managed, a continuous increase of the so‐called “cardiometabolic risk” is noted. Starting from this century, the nomenclature “metabolic syndrome” has become more popular to identify a cluster of disorders including obesity, dyslipidemia, hypertension, and insulin resistance. It is a primary risk factor for diabetes and cardiovascular disease in both genders. Interestingly, the metabolic diseases display a distinct gender disparity with an apparent “female advantage” in the premenopausal women compared with age‐matched men. However, women usually lose such “sex protection” following menopause or affliction of metabolic syndrome especially insulin resistance. A controversy exists in the medical literature concerning whether metabolic syndrome is a real syndrome or simply a cluster of risk factors. Several scenarios are speculated to contribute to the gender dimorphism in the cardiovascular sequelae in patients with metabolic syndrome including sex hormones, intrinsic organ function, and the risk factor profile (e.g., hypertension, dyslipidemia, obesity, sedentary lifestyle, and atherogenic diet). With the alarming rise of obesity prevalence, heart problems in metabolic syndrome continue to rise with a distinct gender dimorphism. Although female hearts seem to better tolerate the stress insults compared with the male counterparts, the female sex hormones such as estrogen can interact with certain risk factors to precipitate myopathic changes in the hearts. This synthetic review of recent literature suggests a role of gender disparity in myopathic factors and risk attributable to each metabolic component in the different prevalence of metabolic syndrome.     

Sex Differences in the Relationship between Asthma and Overweight in Dutch Children: a Survey Study

Objective

Obesity has been identified as a risk factor for asthma in children. However, in the Netherlands, the obesity prevalence is rising while the asthma prevalence in children is stabilising. The aim of this study is to clarify the association between asthma and Body Mass Index (BMI) in children and whether this association is influenced by sex.

Study Design

Parents of 39,316 children (6-16 years) in the south of the Netherlands were invited to complete an online questionnaire on respiratory symptoms, anthropometric variables and several potential confounding factors for asthma and obesity (including sex, birth weight and breastfeeding). Data was analysed by multivariable logistic regression models and an ordinal regression model.

Results

The response rate was 24% (n boys= 4,743, n girls= 4,529). The prevalence of asthma, overweight and obesity was 8%, 15% and 2% respectively. Body mass index - standard deviation Score (BMI-SDS) was related to current asthma (adjusted OR: 1.29; 95%CI: 1.14-1.45, p≤0.001). When stratified for sex, asthma and BMI-SDS were only related in girls (Girls: adjusted OR: 1.31; 95%CI: 1.13-1.51, p≤0.001. Boys: adjusted OR: 1.01; 95%CI: 0.91-1.14, p=0.72).

Conclusions

The positive association between BMI-SDS and asthma is only present in girls, not boys. Future studies into obesity and asthma should correct for sex in their analyses.     

The developmental origins of obesity and related health disorders--prenatal and perinatal factors

Obesity, and its health-related sequelae (the metabolic syndrome), have recently emerged as a global health crisis. The prevalence of childhood and adult obesity in economically developed and developing countries world-wide has more than doubled over the past decade. While genetic factors, increasingly sedentary lifestyles, and overnutrition have all been cited as important components of the obesity crisis, recent epidemiological and experimental evidence suggests that developmental factors--especially those that occur in utero and during early postnatal life--play a significant role in the pandemic. Research into the 'developmental origins of health and disease' (DOHaD) has now firmly established that pre- and perinatal developmental perturbations which predispose to obesity in adult life can result from a variety of factors, including both nutritional surplus and deficiency, and there is growing evidence that these physiological traits can be passed on epigenetically to subsequent generations. Anthropological perspectives regarding the developmental origins of obesity and its related health problems cannot only shed further light on contemporary ethnic human health disparities, but can offer unique insights into the relevance of the developmental origins of disease to community-based public health interventions.     

The increase in the prevalence of asthma and allergy: food for thought

Since about 1960, the prevalence of asthma and allergic disease has increased sufficiently to become a major public-health concern. Concurrently, there have been marked changes in our diet, and it has been proposed that these changes have contributed to the increase in the prevalence of asthma and allergy. In this article, these hypotheses about diet are described, together with the postulated mechanisms and the evidence for and against, leading to the most recent evidence indicating that maternal diet during pregnancy might be particularly important in the development of childhood asthma.     

Breastfeeding and the risk of childhood obesity

Breastfeeding is suggested to be a potential obesity prevention strategy, but the evidence that breast-fed infants have a lower risk of later obesity is equivocal. Fourteen studies published between 2003 and 2006 that considered the relationship between breastfeeding and risk of childhood overweight and obesity were reviewed. Three studies reported a protective effect in children (i.e., increased duration of breastfeeding was associated with a lower risk of childhood overweight/obesity), 4 reported a partial protective effect (i.e., only evident in a subgroup), 6 reported no protective effect, and 1 reported a protective effect in children but not in adults. While there is some evidence that breastfeeding may help to prevent childhood obesity, it should not be viewed as the only preventative nutrition measure. In the U.S., rates of breastfeeding have risen while rates for childhood obesity have increased dramatically. This finding reinforces the view that many factors are involved in maintaining a healthy body weight.     

Diet and asthma: looking back,moving forward

Asthma is an increasing global health burden, especially in the western world. Public health interventions are sought to lessen its prevalence or severity, and diet and nutrition have been identified as potential factors. With rapid changes in diet being one of the hallmarks of westernization, nutrition may play a key role in affecting the complex genetics and developmental pathophysiology of asthma. The present review investigates hypotheses about hygiene, antioxidants, lipids and other nutrients, food types and dietary patterns, breastfeeding, probiotics and intestinal microbiota, vitamin D, maternal diet, and genetics. Early hypotheses analyzed population level trends and focused on major dietary factors such as antioxidants and lipids. More recently, larger dietary patterns beyond individual nutrients have been investigated such as obesity, fast foods, and the Mediterranean diet. Despite some promising hypotheses and findings, there has been no conclusive evidence about the role of specific nutrients, food types, or dietary patterns past early childhood on asthma prevalence. However, diet has been linked to the development of the fetus and child. Breastfeeding provides immunological protection when the infant''s immune system is immature and a modest protective effect against wheeze in early childhood. Moreover, maternal diet may be a significant factor in the development of the fetal airway and immune system. As asthma is a complex disease of gene-environment interactions, maternal diet may play an epigenetic role in sensitizing fetal airways to respond abnormally to environmental insults. Recent hypotheses show promise in a biological approach in which the effects of dietary factors on individual physiology and immunology are analyzed before expansion into larger population studies. Thus, collaboration is required by various groups in studying this enigma from epidemiologists to geneticists to immunologists. It is now apparent that this multidisciplinary approach is required to move forward and understand the complexity of the interaction of dietary factors and asthma.     

Risk factors prevalence for cardiovascular diseases among atomic power industry enterprises personnel

A selective cross-sectional study based on Regional Medico-Dosimetric Register was carried out in some Siberian Group of Chemical Enterprises (SGCE) workers (aged 40-50) with the aim of studying the most important risk factors prevalence for cardiovascular diseases development. 2010 persons examined with the use of standardized epidemiological methods made up 32.6% of total SGCE personnel aged 40-50. Purpose: the study of risk factors of cardiovascular diseases, their prevalence, intensity and significance in atomic power plants workers exposed to occupational long-term ionizing radiation in a "low" dose range (cumulative doses in the range up to 1 Sv). The study of prevalence of risk factors for CVDs development in men occupationally exposed to ionizing radiation revealed frequent changes in the type of work performed, higher levels of psychoemotional tension, as well as high prevalence of low levels of high-density lipoprotein cholesterol (HDL-cholesterol) and obesity. Women workers of the main production were found to have hypercholesterolaemia more often than those of the auxiliary production. Annual health checks of nuclear workers should be extended to include waist and hips measurement, body mass index (BMI) calculation, lipid factors evaluation, as well as stress tests (bicycle and/or stress echocardiography) in case there are three or more risk factors for CVDs for workers of the main production.     

Genetics of asthma: a molecular biologist perspective

Viruses are the predominant infectious cause of asthma exacerbations in the developed world. In addition, recent evidence strongly suggests that viral infections may also have a causal role in the development of childhood asthma. In this article, we will briefly describe the general perception of how the link between infections and asthma has changed over the last century, and then focus on very recent developments that have provided new insights into the contribution of viruses to asthma pathogenesis. Highlighted areas include the contribution of severe early life viral infections to asthma inception, genetic determinants of severe viral infections in infancy, the differences in innate and adaptive immune system cytokine responses to viral infection between asthmatic and nonasthmatic subjects, and a potential vaccine strategy to prevent severe early life virally-induced illness.     

A Common 16p11.2 Inversion Underlies the Joint Susceptibility to Asthma and Obesity

The prevalence of asthma and obesity is increasing worldwide, and obesity is a well-documented risk factor for asthma. The mechanisms underlying this association and parallel time trends remain largely unknown but genetic factors may be involved. Here, we report on a common ∼0.45 Mb genomic inversion at 16p11.2 that can be accurately genotyped via SNP array data. We show that the inversion allele protects against the joint occurrence of asthma and obesity in five large independent studies (combined sample size of 317 cases and 543 controls drawn from a total of 5,809 samples; combined OR = 0.48, p = 5.5 × 10⁻⁶). Allele frequencies show remarkable worldwide population stratification, ranging from 10% in East Africa to 49% in Northern Europe, consistent with discordant and extreme genetic drifts or adaptive selections after human migration out of Africa. Inversion alleles strongly correlate with expression levels of neighboring genes, especially TUFM (p = 3.0 × 10⁻⁴⁰) that encodes a mitochondrial protein regulator of energy balance and inhibitor of type 1 interferon, and other candidates for asthma (IL27) and obesity (APOB48R and SH2B1). Therefore, by affecting gene expression, the ∼0.45 Mb 16p11.2 inversion provides a genetic basis for the joint susceptibility to asthma and obesity, with a population attributable risk of 39.7%. Differential mitochondrial function and basal energy balance of inversion alleles might also underlie the potential selection signature that led to their uneven distribution in world populations.     

The genetics of childhood obesity and interaction with dietary macronutrients

The genes contributing to childhood obesity are categorized into three different types based on distinct genetic and phenotypic characteristics. These types of childhood obesity are represented by rare monogenic forms of syndromic or non-syndromic childhood obesity, and common polygenic childhood obesity. In some cases, genetic susceptibility to these forms of childhood obesity may result from different variations of the same gene. Although the prevalence for rare monogenic forms of childhood obesity has not increased in recent times, the prevalence of common childhood obesity has increased in the United States and developing countries throughout the world during the past few decades. A number of recent genome-wide association studies and mouse model studies have established the identification of susceptibility genes contributing to common childhood obesity. Accumulating evidence suggests that this type of childhood obesity represents a complex metabolic disease resulting from an interaction with environmental factors, including dietary macronutrients. The objective of this article is to provide a review on the origins, mechanisms, and health consequences of obesity susceptibility genes and interaction with dietary macronutrients that predispose to childhood obesity. It is proposed that increased knowledge of these obesity susceptibility genes and interaction with dietary macronutrients will provide valuable insight for individual, family, and community preventative lifestyle intervention, and eventually targeted nutritional and medicinal therapies.     

Childhood Asthma and Mental Retardation

Four hundred consecutive outpatients seen at the Children''s Psychiatric Research Institute, London, Ont., were investigated to determine whether there is a negative correlation between childhood asthma and mental retardation. Of these, 380 were mentally retarded and 20 were of normal intelligence. Only two cases of childhood asthma were found. One of these had an I.Q. of 108 and the other 78, so that no case of asthma was found in the mentally retarded group. On the basis of a reported prevalence rate for asthma of 1.76%, one would expect six or seven cases among the 400. By contrast, among the approximately 800 parents there were 11 cases of chronic asthma, a figure which is approximately the expected number.