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1.  Developmental Profiles of Eczema, Wheeze, and Rhinitis: Two Population-Based Birth Cohort Studies 
PLoS Medicine  2014;11(10):e1001748.
Using data from two population-based birth cohorts, Danielle Belgrave and colleagues examine the evidence for atopic march in developmental profiles for allergic disorders.
Please see later in the article for the Editors' Summary
Background
The term “atopic march” has been used to imply a natural progression of a cascade of symptoms from eczema to asthma and rhinitis through childhood. We hypothesize that this expression does not adequately describe the natural history of eczema, wheeze, and rhinitis during childhood. We propose that this paradigm arose from cross-sectional analyses of longitudinal studies, and may reflect a population pattern that may not predominate at the individual level.
Methods and Findings
Data from 9,801 children in two population-based birth cohorts were used to determine individual profiles of eczema, wheeze, and rhinitis and whether the manifestations of these symptoms followed an atopic march pattern. Children were assessed at ages 1, 3, 5, 8, and 11 y. We used Bayesian machine learning methods to identify distinct latent classes based on individual profiles of eczema, wheeze, and rhinitis. This approach allowed us to identify groups of children with similar patterns of eczema, wheeze, and rhinitis over time.
Using a latent disease profile model, the data were best described by eight latent classes: no disease (51.3%), atopic march (3.1%), persistent eczema and wheeze (2.7%), persistent eczema with later-onset rhinitis (4.7%), persistent wheeze with later-onset rhinitis (5.7%), transient wheeze (7.7%), eczema only (15.3%), and rhinitis only (9.6%). When latent variable modelling was carried out separately for the two cohorts, similar results were obtained. Highly concordant patterns of sensitisation were associated with different profiles of eczema, rhinitis, and wheeze. The main limitation of this study was the difference in wording of the questions used to ascertain the presence of eczema, wheeze, and rhinitis in the two cohorts.
Conclusions
The developmental profiles of eczema, wheeze, and rhinitis are heterogeneous; only a small proportion of children (∼7% of those with symptoms) follow trajectory profiles resembling the atopic march.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Our immune system protects us from viruses, bacteria, and other pathogens by recognizing specific molecules on the invader's surface and initiating a sequence of events that culminates in the death of the pathogen. Sometimes, however, our immune system responds to harmless materials (allergens such as pollen) and triggers allergic, or atopic, symptoms. Common atopic symptoms include eczema (transient dry itchy patches on the skin), wheeze (high pitched whistling in the chest, a symptom of asthma), and rhinitis (sneezing or a runny nose in the absence of a cold or influenza). All these symptoms are very common during childhood, but recent epidemiological studies (examinations of the patterns and causes of diseases in a population) have revealed age-related changes in the proportions of children affected by each symptom. So, for example, eczema is more common in infants than in school-age children. These findings have led to the idea of “atopic march,” a natural progression of symptoms within individual children that starts with eczema, then progresses to wheeze and finally rhinitis.
Why Was This Study Done?
The concept of atopic march has led to the initiation of studies that aim to prevent the development of asthma in children who are thought to be at risk of asthma because they have eczema. Moreover, some guidelines recommend that clinicians tell parents that children with eczema may later develop asthma or rhinitis. However, because of the design of the epidemiological studies that support the concept of atopic march, children with eczema who later develop wheeze and rhinitis may actually belong to a distinct subgroup of children, rather than representing the typical progression of atopic diseases. It is important to know whether atopic march adequately describes the natural history of atopic diseases during childhood to avoid the imposition of unnecessary strategies on children with eczema to prevent asthma. Here, the researchers use machine learning techniques to model the developmental profiles of eczema, wheeze, and rhinitis during childhood in two large population-based birth cohorts by taking into account time-related (longitudinal) changes in symptoms within individuals. Machine learning is a data-driven approach that identifies structure within the data (for example, a typical progression of symptoms) using unsupervised learning of latent variables (variables that are not directly measured but are inferred from other observable characteristics).
What Did the Researchers Do and Find?
The researchers used data from two UK birth cohorts—the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Manchester Asthma and Allergy Study (MAAS)—for their study (9,801 children in total). Both studies enrolled children at birth and monitored their subsequent health at regular review clinics. At each review clinic, information about eczema, wheeze, and rhinitis was collected from the parents using validated questionnaires. The researchers then used these data and machine learning methods to identify groups of children with similar patterns of onset of eczema, wheeze, and rhinitis over the first 11 years of life. Using a type of statistical model called a latent disease profile model, the researchers found that the data were best described by eight latent classes—no disease (51.3% of the children), atopic march (3.1%), persistent eczema and wheeze (2.7%), persistent eczema with later-onset rhinitis (4.7%), persistent wheeze with later-onset rhinitis (5.7%), transient wheeze (7.7%), eczema only (15.3%), and rhinitis only (9.6%).
What Do These Findings Mean?
These findings show that, in two large UK birth cohorts, the developmental profiles of eczema, wheeze, and rhinitis were heterogeneous. Most notably, the progression of symptoms fitted the profile of atopic march in fewer than 7% of children with symptoms. The researchers acknowledge that their study has some limitations. For example, small differences in the wording of the questions used to gather information from parents about their children's symptoms in the two cohorts may have slightly affected the findings. However, based on their findings, the researchers propose that, because eczema, wheeze, and rhinitis are common, these symptoms often coexist in individuals, but as independent entities rather than as a linked progression of symptoms. Thus, using eczema as an indicator of subsequent asthma risk and assigning “preventative” measures to children with eczema is flawed. Importantly, clinicians need to understand the heterogeneity of patterns of atopic diseases in children and to communicate this variability to parents when advising them about the development and resolution of atopic symptoms in their children.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001748.
The UK National Health Service Choices website provides information about eczema (including personal stories), asthma (including personal stories), and rhinitis
The US National Institute of Allergy and Infectious Diseases provides information about atopic diseases
The UK not-for-profit organization Allergy UK provides information about atopic diseases and a description of the atopic march
MedlinePlus encyclopedia has pages on eczema, wheezing, and rhinitis (in English and Spanish)
MedlinePlus provides links to further resources about allergies, eczema, and asthma (in English and Spanish)
Information about ALSPAC and MAAS is available
Wikipedia has pages on machine learning and latent disease profile models (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1001748
PMCID: PMC4204810  PMID: 25335105
2.  Adult-Onset Asthma Becomes the Dominant Phenotype among Women by Age 40 Years. The Longitudinal CARDIA Study 
Rationale: Although asthma is usually considered to originate in childhood, adult-onset disease is being increasingly reported.
Objectives: To contrast the proportion and natural history of adult-onset versus pediatric-onset asthma in a community-based cohort. We hypothesized that asthma in women is predominantly of adult onset rather than of pediatric onset.
Methods: This study used data from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort in the United States over a 25-year period. Adult- and pediatric-onset asthma phenotypes were studied, as defined by age at onset of 18 years or older. Subjects with asthma were categorized by sex, obesity, atopy, smoking, and race by mean age/examination year, using a three-way analysis of covariance model. Natural history of disease was examined using probabilities derived from a Markov chain model.
Measurements and Main Results: Asthma of adult onset became the dominant (i.e., exceeded 50%) phenotype in women by age 40 years. The age by which adult-onset asthma became the dominant phenotype was further lowered for obese, nonatopic, ever-smoking, or white women. The prevalence trend with increasing time for adult-onset disease was greater among subjects with nonatopic than atopic asthma among both sexes. Furthermore, adult-onset asthma had remarkable sex-related differences in risk factors. In both sexes, the quiescent state for adult-onset asthma was less frequent and also “less stable” over time than for pediatric-onset asthma.
Conclusions: Using a large national cohort, this study challenges the dictum that most asthma in adults originates in childhood. Studies of the differences between pediatric- and adult-onset asthma may provide greater insight into the phenotypic heterogeneity of asthma.
doi:10.1513/AnnalsATS.201212-115OC
PMCID: PMC3960903  PMID: 23802814
adult-onset; pediatric-onset; obesity; nonatopic; recrudescent
3.  Prognostic factors for the outcome of childhood asthma in adolescence. 
Thorax  1996;51(Suppl 1):S7-12.
By the second decade of life asthma symptoms often abate and it may seem that patients with mild asthma have "outgrown" the disease. Unfortunately this is likely to be the exception rather than the rule. Although the severity of asthma symptoms fluctuates with time, the inherited tendency towards respiratory symptoms never disappears and many teenagers who seem to be free of symptoms do, in fact, have persistent asthma. During symptom-free periods subclinical, but nevertheless significant, airways obstruction and/or bronchial hyperresponsiveness may be present. It is not unusual for adults who have been asymptomatic for a number of years to redevelope asthma symptoms. Indeed, much of the so-called adult onset asthma has its roots in childhood. Levison concluded that, in these subjects, it is often not the asthma that is outgrown but the paediatrician. The more severe astham is in childhood the more likely it is that the disease will persist in adulthood. A complete list of the characteristics of the disease in childhood, and the potential risk factors associated with an unfavourable prognosis, such as pulmonary function and bronchial responsiveness and markers of airway inflammation, is therefore needed. As properly matched and controlled prospective long term studies have not been published it has not been possible to evaluate the effects on prognosis of any single class of antiasthma agent. Such studies are needed to find out if it is possible to alter the natural history of the disease. In theory modern asthma treatments, because they are able to improve symptoms and underlying disease phenomena, are also beneficial in the long term prognosis of childhood asthma. The majority of patients with persistent asthma included in the currently available studies were not receiving adequate treatment. Since compliance with therapeutic regimens in asthma, especially in adolescence, is low, a monitoring system is needed to guarantee adequate follow up and treatment during and beyond puberty.
PMCID: PMC1129003  PMID: 8658386
4.  PEDIATRIC ASTHMA: NATURAL HISTORY, ASSESSMENT AND TREATMENT 
Wheezing and childhood asthma are not synonymous but rather comprise a heterogeneous group of conditions that have different outcomes over the course of childhood. Most infants who wheeze have a transient condition associated with diminished airway function at birth and have no increased risk of asthma later in life. However, children with persistent wheezing throughout childhood and frequent exacerbations represent the main challenge today. Studying the natural history of asthma is important for the understanding and accurate prediction of the clinical course of different phenotypes. To date, a great improvement has been achieved in reducing the frequency of asthma symptoms. However, neither decreased environmental exposure nor controller treatment, as recommended by the recent national asthma education and prevention program, can halt the progression of asthma in childhood or the development of persistent wheezing phenotype. This review focuses on the recent studies that led to the current understanding of asthma phenotypes in childhood and the recommended treatments.
doi:10.1002/msj.20285
PMCID: PMC3172616  PMID: 21913196
asthma; pediatric; phenotypes; exacerbation; treatment; inhaled corticosteroid (ICS); short acting beta agonist (SABA); long acting beta agonist (LABA)
5.  Developing Asthma in Childhood from Exposure to Secondhand Tobacco Smoke: Insights from a Meta-Regression 
Environmental Health Perspectives  2007;115(10):1394-1400.
Objective
Studies have identified associations between household secondhand tobacco smoke (SHS) exposure and induction of childhood asthma. However, the true nature and strength of this association remains confounded in many studies, producing inconsistent evidence. To look for sources of potential bias and try to uncover consistent patterns of relative risk estimates (RRs), we conducted a meta-analysis of studies published between 1970 and 2005.
Data sources
Through an extensive literature search, we identified 38 epidemiologic studies of SHS exposure and the development of childhood asthma (that also controlled for atopy history) from 300 potentially relevant articles.
Data synthesis
We observed substantial heterogeneity within initial summary RRs of 1.48 [95% confidence interval (CI), 1.32–1.65], 1.25 (1.21–1.30), and 1.21 (1.08–1.36), for ever, current, and incident asthma, respectively. Lack of control for type of atopy history (familial or child) and child’s own smoking status within studies and age category altered summary RRs in separate meta-regressions. After adjusting for these confounding characteristics, consistent patterns of association emerged between SHS exposure and childhood asthma induction. Our summary RR of 1.33 (95% CI, 1.14–1.56) from studies of incident asthma among older children (6–18 years of age) is 1.27 times the estimate from studies of younger children and higher than estimates reported in earlier meta-analyses.
Conclusions
This new finding indicates that exposure duration may be a more important factor in the induction of asthma than previously understood, and suggests that SHS could be a more fundamental and widespread cause of childhood asthma than some previous meta-analyses have indicated.
doi:10.1289/ehp.10155
PMCID: PMC2022647  PMID: 17938726
childhood asthma; environmental tobacco smoke; ETS; meta-analysis; meta-regression; relative risk; secondhand tobacco smoke; SHS
6.  Pediatric Asthma 
Asthma currently affects the lives of more than 30 million Americans from infancy to the elderly. In many ways, pediatric asthma differs from adult asthma, including childhood-onset adult asthma. Despite many advances in our understanding of the disease, the natural history of asthma is not well defined, especially in different subsets of patients. For many with allergic asthma the disease has its origins in early childhood, associated with early sensitization to aeroallergens and exposure to repeated viral infections. These early life exposures, coupled with genetically determined susceptibility, have a major impact on the natural history of the disease. A number of risk factors during the critical early stages in the initiation of asthma have been associated with subsequent outcomes. In addition, protective factors linked to early life experiences have also been delineated which may impact the development of atopy and asthma and reduce the prevalence of these diseases. Cumulatively, the data highlight the critical nature of this early period in which immune/inflammatory responses in the lung are initiated and serve to maintain the disease in subsequent years.
doi:10.1513/pats.200808-090RM
PMCID: PMC2677403  PMID: 19387030
asthma; children; predictors; persistence
7.  Association of Adenotonsillectomy with Asthma Outcomes in Children: A Longitudinal Database Analysis 
PLoS Medicine  2014;11(11):e1001753.
Rakesh Bhattacharjee and colleagues use data from a US private health insurance database to compare asthma severity measures in children one year before and one year after they underwent adenotonsillectomy with asthma measures in those who did not undergo adenotonsillectomy.
Please see later in the article for the Editors' Summary
Background
Childhood asthma and obstructive sleep apnea (OSA), both disorders of airway inflammation, were associated in recent observational studies. Although childhood OSA is effectively treated by adenotonsillectomy (AT), it remains unclear whether AT also improves childhood asthma. We hypothesized that AT, the first line of therapy for childhood OSA, would be associated with improved asthma outcomes and would reduce the usage of asthma therapies in children.
Methods and Findings
Using the 2003–2010 MarketScan database, we identified 13,506 children with asthma in the United States who underwent AT. Asthma outcomes during 1 y preceding AT were compared to those during 1 y following AT. In addition, 27,012 age-, sex-, and geographically matched children with asthma without AT were included to examine asthma outcomes among children without known adenotonsillar tissue morbidity. Primary outcomes included the occurrence of a diagnostic code for acute asthma exacerbation (AAE) or acute status asthmaticus (ASA). Secondary outcomes included temporal changes in asthma medication prescriptions, the frequency of asthma-related emergency room visits (ARERs), and asthma-related hospitalizations (ARHs). Comparing the year following AT to the year prior, AT was associated with significant reductions in AAE (30.2%; 95% CI: 25.6%–34.3%; p<0.0001), ASA (37.9%; 95% CI: 29.2%–45.6%; p<0.0001), ARERs (25.6%; 95% CI: 16.9%–33.3%; p<0.0001), and ARHs (35.8%; 95% CI: 19.6%–48.7%; p = 0.02). Moreover, AT was associated with significant reductions in most asthma prescription refills, including bronchodilators (16.7%; 95% CI: 16.1%–17.3%; p<0.001), inhaled corticosteroids (21.5%; 95% CI: 20.7%–22.3%; p<0.001), leukotriene receptor antagonists (13.4%; 95% CI: 12.9%–14.0%; p<0.001), and systemic corticosteroids (23.7%; 95% CI: 20.9%–26.5%; p<0.001). In contrast, there were no significant reductions in these outcomes in children with asthma who did not undergo AT over an overlapping follow-up period. Limitations of the MarketScan database include lack of information on race and obesity status. Also, the MarketScan database does not include information on children with public health insurance (i.e., Medicaid) or uninsured children.
Conclusions
In a very large sample of privately insured children, AT was associated with significant improvements in several asthma outcomes. Contingent on validation through prospectively designed clinical trials, this study supports the premise that detection and treatment of adenotonsillar tissue morbidity may serve as an important strategy for improving asthma control.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The global burden of asthma has been rising steadily over the past few decades. Nowadays, about 200–300 million adults and children worldwide are affected by asthma, a chronic condition caused by inflammation of the airways (the tubes that carry air in and out of the lungs). Although asthma can develop at any age, it is often diagnosed in childhood—asthma is one of the commonest chronic diseases in children. In the US, for example, asthma affects around 7.1 million children under the age of 18 years and is the third leading cause of hospitalization of children under the age of 15 years. In people with asthma, the airways can react very strongly to allergens such as animal fur or to irritants such as cigarette smoke. Exercise, cold air, and infections can trigger asthma attacks, which can be fatal. The symptoms of asthma include wheezing, coughing, chest tightness, and shortness of breath. Asthma cannot be cured, but drugs can relieve its symptoms and prevent acute asthma attacks.
Why Was This Study Done?
Recent studies have found an association between severe childhood asthma and obstructive sleep apnea (OSA). In OSA, airway inflammation promotes hypertrophy (excess growth) of the adenoids and the tonsils, immune system tissues in the upper airway. During sleep, the presence of hypertrophic adenotonsillar tissues predisposes the walls of the throat to collapse, which results in apnea—a brief interruption in breathing. People with OSA often snore loudly and frequently wake from deep sleep as they struggle to breathe. Childhood OSA, which affects 2%–3% of children, can be effectively treated by removal of the adenoids and tonsils (adenotonsillectomy). Given the association between childhood OSA and severe asthma and given the involvement of airway inflammation in both conditions, might adenotonsillectomy also improve childhood asthma? Here, the researchers analyze data from the MarketScan database, a large database of US patients with private health insurance, to investigate whether adenotonsillectomy is associated with improvements in asthma outcomes and with reductions in the use of asthma therapies in children.
What Did the Researchers Do and Find?
The researchers used the database to identify 13,506 children with asthma who had undergone adenotonsillectomy and to obtain information about asthma outcomes among these children for the year before and the year after the operation. Because asthma severity tends to decrease with age, the researchers also used the database to identify 27,012 age-, sex-, and geographically matched children with asthma who did not have the operation so that they could examine asthma outcomes over an equivalent two-year period in the absence of complications related to adenotonsillar hypertrophy. Comparing the year after adenotonsillectomy with the year before the operation, adenotonsillectomy was associated with a 30% reduction in acute asthma exacerbations, a 37.9% reduction in acute status asthmaticus (an asthma attack that is unresponsive to the drugs usually used to treat attacks), a 25.6% reduction in asthma-related emergency room visits, and a 35.8% reduction in asthma-related hospitalizations. By contrast, among the control children, there was only a 2% reduction in acute asthma exacerbations and only a 7% reduction in acute status asthmaticus over an equivalent two-year period. Adenotonsillectomy was also associated with significant reductions (changes unlikely to have occurred by chance) in prescription refills for most types of drugs used to treat asthma, whereas there were no significant reductions in prescription refills among children with asthma who had not undergone adenotonsillectomy. The study was limited by the lack of measures of race and obesity, which are both associated with severity of asthma.
What Do These Findings Mean?
These findings show that in a large sample of privately insured children in the US, adenotonsillectomy was associated with significant improvements in several asthma outcomes. These results do not show, however, that adenotonsillectomy caused a reduction in the severity of childhood asthma. It could be that the children who underwent adenotonsillectomy (but not those who did not have the operation) shared another unknown factor that led to improvements in their asthma over time. To prove a causal link, it will be necessary to undertake a randomized controlled trial in which the outcomes of groups of children with asthma who are chosen at random to undergo or not undergo adenotonsillectomy are compared. However, with the proviso that there are some risks associated with adenotonsillectomy, these findings suggest that the detection and treatment of adenotonsillar hypertrophy may help to improve asthma control in children.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001753.
The US Centers for Disease Control and Prevention provides information on asthma, including videos, games, and links to other resources for children with asthma
The American Lung Association provides detailed information about asthma and a fact sheet on asthma in children; it also has information about obstructive sleep apnea
The National Sleep Foundation provides information on snoring and obstructive sleep apnea in children
The UK National Health Service Choices website provides information (including some personal stories) about asthma, about asthma in children, and about obstructive sleep apnea
The “Global Asthma Report 2014” will be available in October 2014
MedlinePlus provides links to further information on asthma, on asthma in children, on sleep apnea, and on tonsils and adenoids (in English and Spanish)
doi:10.1371/journal.pmed.1001753
PMCID: PMC4219664  PMID: 25369282
8.  Effects of BMI, Fat Mass, and Lean Mass on Asthma in Childhood: A Mendelian Randomization Study 
PLoS Medicine  2014;11(7):e1001669.
In this study, Granell and colleagues used Mendelian randomization to investigate causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ years in the Avon Longitudinal Study of Parents and Children (ALSPAC) and found that higher BMI increases the risk of asthma in mid-childhood.
Please see later in the article for the Editors' Summary
Background
Observational studies have reported associations between body mass index (BMI) and asthma, but confounding and reverse causality remain plausible explanations. We aim to investigate evidence for a causal effect of BMI on asthma using a Mendelian randomization approach.
Methods and Findings
We used Mendelian randomization to investigate causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ y in the Avon Longitudinal Study of Parents and Children (ALSPAC). A weighted allele score based on 32 independent BMI-related single nucleotide polymorphisms (SNPs) was derived from external data, and associations with BMI, fat mass, lean mass, and asthma were estimated. We derived instrumental variable (IV) estimates of causal risk ratios (RRs). 4,835 children had available data on BMI-associated SNPs, asthma, and BMI. The weighted allele score was strongly associated with BMI, fat mass, and lean mass (all p-values<0.001) and with childhood asthma (RR 2.56, 95% CI 1.38–4.76 per unit score, p = 0.003). The estimated causal RR for the effect of BMI on asthma was 1.55 (95% CI 1.16–2.07) per kg/m2, p = 0.003. This effect appeared stronger for non-atopic (1.90, 95% CI 1.19–3.03) than for atopic asthma (1.37, 95% CI 0.89–2.11) though there was little evidence of heterogeneity (p = 0.31). The estimated causal RRs for the effects of fat mass and lean mass on asthma were 1.41 (95% CI 1.11–1.79) per 0.5 kg and 2.25 (95% CI 1.23–4.11) per kg, respectively. The possibility of genetic pleiotropy could not be discounted completely; however, additional IV analyses using FTO variant rs1558902 and the other BMI-related SNPs separately provided similar causal effects with wider confidence intervals. Loss of follow-up was unlikely to bias the estimated effects.
Conclusions
Higher BMI increases the risk of asthma in mid-childhood. Higher BMI may have contributed to the increase in asthma risk toward the end of the 20th century.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The global burden of asthma, a chronic (long-term) condition caused by inflammation of the airways (the tubes that carry air in and out of the lungs), has been rising steadily over the past few decades. It is estimated that, nowadays, 200–300 million adults and children worldwide are affected by asthma. Although asthma can develop at any age, it is often diagnosed in childhood—asthma is the most common chronic disease in children. In people with asthma, the airways can react very strongly to allergens such as animal fur or to irritants such as cigarette smoke, becoming narrower so that less air can enter the lungs. Exercise, cold air, and infections can also trigger asthma attacks, which can be fatal. The symptoms of asthma include wheezing, coughing, chest tightness, and shortness of breath. Asthma cannot be cured, but drugs can relieve its symptoms and prevent acute asthma attacks.
Why Was This Study Done?
We cannot halt the ongoing rise in global asthma rates without understanding the causes of asthma. Some experts think obesity may be one cause of asthma. Obesity, like asthma, is increasingly common, and observational studies (investigations that ask whether individuals exposed to a suspected risk factor for a condition develop that condition more often than unexposed individuals) in children have reported that body mass index (BMI, an indicator of body fat calculated by dividing a person's weight in kilograms by their height in meters squared) is positively associated with asthma. Observational studies cannot prove that obesity causes asthma because of “confounding.” Overweight children with asthma may share another unknown characteristic (confounder) that actually causes both obesity and asthma. Moreover, children with asthma may be less active than unaffected children, so they become overweight (reverse causality). Here, the researchers use “Mendelian randomization” to assess whether BMI has a causal effect on asthma. In Mendelian randomization, causality is inferred from associations between genetic variants that mimic the effect of a modifiable risk factor and the outcome of interest. Because gene variants are inherited randomly, they are not prone to confounding and are free from reverse causation. So, if a higher BMI leads to asthma, genetic variants associated with increased BMI should be associated with an increased risk of asthma.
What Did the Researchers Do and Find?
The researchers investigated causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ years in 4,835 children enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC, a long-term health project that started in 1991). They calculated an allele score for each child based on 32 BMI-related genetic variants, and estimated associations between this score and BMI, fat mass and lean mass (both measured using a special type of X-ray scanner; in children BMI is not a good indicator of “fatness”), and asthma. They report that the allele score was strongly associated with BMI, fat mass, and lean mass, and with childhood asthma. The estimated causal relative risk (risk ratio) for the effect of BMI on asthma was 1.55 per kg/m2. That is, the relative risk of asthma increased by 55% for every extra unit of BMI. The estimated causal relative risks for the effects of fat mass and lean mass on asthma were 1.41 per 0.5 kg and 2.25 per kg, respectively.
What Do These Findings Mean?
These findings suggest that a higher BMI increases the risk of asthma in mid-childhood and that global increases in BMI toward the end of the 20th century may have contributed to the global increase in asthma that occurred at the same time. It is possible that the observed association between BMI and asthma reported in this study is underpinned by “genetic pleiotropy” (a potential limitation of all Mendelian randomization analyses). That is, some of the genetic variants included in the BMI allele score could conceivably also increase the risk of asthma. Nevertheless, these findings suggest that public health interventions designed to reduce obesity may also help to limit the global rise in asthma.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001669.
The US Centers for Disease Control and Prevention provides information on asthma and on all aspects of overweight and obesity (in English and Spanish)
The World Health Organization provides information on asthma and on obesity (in several languages)
The UK National Health Service Choices website provides information about asthma, about asthma in children, and about obesity (including real stories)
The Global Asthma Report 2011 is available
The Global Initiative for Asthma released its updated Global Strategy for Asthma Management and Prevention on World Asthma Day 2014
Information about the Avon Longitudinal Study of Parents and Children is available
MedlinePlus provides links to further information on obesity in children, on asthma, and on asthma in children (in English and Spanish
Wikipedia has a page on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1001669
PMCID: PMC4077660  PMID: 24983943
9.  Allergic diseases and asthma in the family predict the persistence and onset-age of asthma: a prospective cohort study 
Respiratory Research  2014;15(1):152.
Background
Family history of asthma and other allergic diseases have been linked to the risk of childhood asthma previously, but little is known about their effect on the age-of-onset and persistency of asthma until young adulthood.
Methods
We assessed the effect of the family history of asthma and allergic diseases on persistent vs. transient, and early- vs. late-onset persistent asthma in The Espoo Cohort Study 1991–2011, a population-based cohort study of 1623 subjects (follow-up rate 63.2%). The determinants were any family history (any parent or sibling); maternal; paternal; siblings only; parents only; and both siblings and parents. Analyses were conducted separately for asthma and allergic diseases while taking the other disease into account as a confounding factor. The outcomes were persistent, transient, early-onset persistent (<13 years) and late-onset persistent asthma. Adjusted risk ratios (RR) were calculated applying Poisson regression. Q-statistics were used to assess heterogeneity between RRs.
Results
Family history was associated with the different subtypes but the magnitude of effect varied quantitatively. Any family history of asthma was a stronger determinant of persistent (adjusted RR = 2.82, 95% CI 1.99-4.00) than transient asthma (1.65, 1.03-2.65) (heterogeneity: P = 0.07) and on early-onset than late-onset persistent asthma. Also any family history of allergic diseases was a stronger determinant of persistent and early-onset asthma. The impact of paternal asthma continued to young adulthood (early-onset: 3.33, 1.57-7.06 vs. late-onset 2.04, 0.75-5.52) while the influence of maternal asthma decreased with age (Early-onset 3.94, 2.11-7.36 vs. Late-onset 0.88, 0.28-2.81). Paternal allergic diseases did not follow the pattern of paternal asthma, since they showed no association with late-onset asthma. Also the effect estimates for other subtypes were lower than in other hereditary groups (persistent 1.29, 0.75-2.22 vs. transient 1.20, 0.67-2.15 and early-onset 1.86, 0.95-3.64 vs. late-onset 0.64, 0.22-1.80).
Conclusions
Family history of asthma and allergic diseases are strong determinants of asthma, but the magnitude of effect varies according to the hereditary group so that some subtypes have a stronger hereditary component, and others may be more strongly related to environmental exposures. Our results provide useful information for assessing the prognosis of asthma based on a thorough family history.
doi:10.1186/s12931-014-0152-8
PMCID: PMC4255429  PMID: 25427760
Asthma; Allergic diseases; Family history; Heredity; Cohort study; Risk ratio; Longitudinal study; Heterogeneity; Epidemiology; Age of onset
10.  Factors in childhood as predictors of asthma in adult life. 
BMJ : British Medical Journal  1994;309(6947):90-93.
OBJECTIVE--To determine which factors measured in childhood predict asthma in adult life. DESIGN--Prospective study over 25 years of a birth cohort initially studied at the age of 7. SETTING--Tasmania, Australia. SUBJECTS--1494 men and women surveyed in 1991-3 when aged 29 to 32 (75% of a random stratified sample from the 1968 Tasmanian asthma survey of children born in 1961 and at school in Tasmania). MAIN OUTCOME MEASURES--Self reported asthma or wheezy breathing in the previous 12 months (current asthma). RESULTS--Of the subjects with asthma or wheezy breathing by the age of 7, as reported by their parents 25.6% (190/741) reported current asthma as an adult compared with 10.8% (81/753) of subjects without parent reported childhood asthma (P < 0.001). Factors measured at the age of 7 that independently predicted current asthma as an adult were being female (odds ratio 1.57; 95% confidence interval 1.19 to 2.08); having a history of eczema (1.45; 1.04 to 2.03); having a low mild forced expiratory flow rate (interquartile odds ratio 1.40; 1.15 to 1.71); having a mother or father with a history of asthma (1.74 (1.23 to 2.47) and 1.68 (1.18 to 2.38) respectively); and having childhood asthma (1.59; 1.10 to 2.29) and, if so, having the first attack after the age of 2 (1.66; 1.17 to 2.36) or having had more than 10 attacks (1.70; 1.17 to 2.48). CONCLUSION--Children with asthma reported by their parents in 1968 were more likely than not to be free of symptoms as adults. The subjects who had more severe asthma (especially if it developed after the age of 2 and was associated with reduced expiratory flow), were female, or had parents who had asthma were at an increased risk of having asthma as an adult. These findings have implications for the treatment and prognosis of childhood asthma, targeting preventive and educational strategies and understanding the onset of asthma in adult life.
PMCID: PMC2540556  PMID: 8038673
11.  Polygenic risk and the development and course of asthma: Evidence from a 4-decade longitudinal study 
The lancet. Respiratory medicine  2013;1(6):453-461.
BACKGROUND
Genome-wide association studies (GWAS) have discovered loci that predispose to asthma. To integrate these new discoveries with emerging models of asthma pathobiology, research is needed to test how genetic discoveries relate to developmental and biological characteristics of asthma.
METHODS
We derived a multi-locus profile of genetic risk from published GWAS of asthma case status. We then tested associations between this “genetic risk score” and developmental and biological characteristics of asthma in a population-based long-running birth cohort, the Dunedin Longitudinal Study (n=1,037). We evaluated asthma onset, persistence, atopy, airway hyperresponsiveness, incompletely reversible airflow obstruction, and asthma-related school and work absenteeism and hospitalization during 9 prospective assessments spanning ages 9–38 years, when 95% of surviving cohort members were seen.
INTERPRETATION
Cohort members at higher genetic risk experienced asthma onset earlier in life (HR=1.12 [1.01–1.26]). Childhood-onset asthma cases at higher genetic risk were more likely to become life-course-persistent asthma cases (RR=1.36 [1.14–1.63]). Asthma cases at higher genetic risk more often manifested atopy (RR=1.07 [1.01–1.14]), airway hyperresponsiveness (RR=1.16 [1.03–1.32]), and incompletely reversible airflow obstruction (RR=1.28 [1.04–1.57]). They were also more likely to miss school or work due to asthma (IRR=1.38 [1.02–1.86]) and to be hospitalized with breathing problems (HR=1.38 [1.07–1.79]). Genotypic information about asthma risk was independent of and additive to information derived from cohort members’ family histories of asthma.
CONCLUSIONS
Findings from this population study confirm that GWAS-discoveries for asthma associate with a childhood-onset phenotype and advance asthma genetics beyond the original GWAS-discoveries in three ways: (1) We show that genetic risks predict which childhood-onset asthma cases remit and which become life-course-persistent cases, although these predictions are not sufficiently sensitive or specific to support immediate clinical translation; (2) We elucidate a biological profile of the asthma that arises from these genetic risks: asthma characterized by atopy and airway hyperresponsiveness and leading to incompletely reversible airflow obstruction; and (3) We describe the real-life impact of GWAS-discoveries by quantifying genetic associations with missed school and work and hospitalization.
doi:10.1016/S2213-2600(13)70101-2
PMCID: PMC3899706  PMID: 24429243
12.  Asthma and allergies in Jamaican children aged 2–17 years: a cross-sectional prevalence survey 
BMJ Open  2012;2(4):e001132.
Objective
To determine the prevalence and severity of asthma and allergies as well as risk factors for asthma among Jamaican children aged 2–17 years.
Design
A cross-sectional, community-based prevalence survey using the International Study of Asthma and Allergies in Childhood questionnaire. The authors selected a representative sample of 2017 children using stratified, multistage cluster sampling design using enumeration districts as primary sampling units.
Setting
Jamaica, a Caribbean island with a total population of approximately 2.6 million, geographically divided into 14 parishes.
Participants
Children aged 2–17 years, who were resident in private households. Institutionalised children such as those in boarding schools and hospitals were excluded from the survey.
Primary and secondary outcome measures
The prevalence and severity of asthma and allergy symptoms, doctor-diagnosed asthma and risk factors for asthma.
Results
Almost a fifth (19.6%) of Jamaican children aged 2–17 years had current wheeze, while 16.7% had self-reported doctor-diagnosed asthma. Both were more common among males than among females. The prevalence of rhinitis, hay fever and eczema among children was 24.5%, 25% and 17.3%, respectively. Current wheeze was more common among children with rhinitis in the last 12 months (44.3% vs 12.6%, p<0.001), hay fever (36.8% vs 13.8%, p<0.001) and eczema (34.1% vs 16.4%, p<0.001). Independent risk factors for current wheeze (ORs, 95% CI) were chest infections in the first year of life 4.83 (3.00 to 7.77), parental asthma 4.19 (2.8 to 6.08), rhinitis in the last 12 months 6.92 (5.16 to 9.29), hay fever 4.82 (3.62 to 6.41), moulds in the home 2.25 (1.16 to 4.45), cat in the home 2.44 (1.66 to 3.58) and dog in the home 1.81 (1.18 to 2.78).
Conclusions
The prevalence of asthma and allergies in Jamaican children is high. Significant risk factors for asthma include chest infections in the first year of life, a history of asthma in the family, allergies, moulds and pets in the home.
Article summary
Article focus
The prevalence of asthma and allergies in both developed and developing countries is continuing to rise.
In some Caribbean countries, asthma is a public health problem associated with high economic costs.
This study determined the prevalence of asthma, allergy symptoms and associated risk factors.
Key messages
We demonstrated that the prevalence of asthma and allergy symptoms among Jamaican children aged 2–17 years is high.
Both the prevalence and severity of asthma symptoms are comparable to that reported among children in high-income countries.
Current wheeze and doctor-diagnosed asthma were more common in males and in children with allergies.
A history of asthma in the family, chest infections in the first year of life, allergies, exposure to moulds and pets in the home were associated with significant risk for asthma.
Identifying children at high risk for asthma and controlling modifiable risk factors is important in reducing the prevalence and morbidity related to asthma.
Strengths and limitations of this study
This is the first national study on asthma and allergies in Jamaica using a nationally representative sample of children with a response rate of 80%.
We used a modified ISAAC protocol in which sampling was done by household rather than by school. Using a population-based sampling strategy; we sampled one child and one adult per household. This approach enabled us to obtain national prevalence estimates for both adults and children in one survey at a reduced cost.
Limitations of this study include the fact that the prevalence of asthma and allergies was based solely on self-reports, no objective measures were done. Also in younger children, caregivers responded to questionnaires.
doi:10.1136/bmjopen-2012-001132
PMCID: PMC3400072  PMID: 22798254
13.  Outcome of children of parents with atopic asthma and transient childhood wheezy bronchitis 
Thorax  1997;52(11):953-957.
BACKGROUND: Childhood asthma and wheeze only in the presence of respiratory infection (wheezy bronchitis) appear to have different prognoses and may differ in their aetiology and heritability. In particular, slight reductions in lung function may be associated with episodes of wheezing associated with intercurrent viral infection. METHODS: Outcomes for wheezing symptoms and lung function were studied in 133 offspring of three distinct groups of 69 middle aged probands with childhood histories of (1) atopic asthma (n = 18), (2) wheeze associated with upper respiratory tract infection (wheezy bronchitis, n = 24), and (3) no symptoms (n = 27). Probands were selected from a previously studied cohort in which outcomes of wheezy bronchitis and asthma had been shown to differ. RESULTS: Children of probands with wheezy bronchitis had a lower prevalence of current wheezing symptoms. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in boys of probands with a history of wheezy bronchitis were significantly reduced compared with either of the other two groups (p < 0.0001). In a multivariate analysis, grouping based on parent proband had a significant effect on lung function, independent of factors such as symptoms, atopy or smoking history. CONCLUSIONS: The different symptomatic and lung function outcome in children of probands with wheezy bronchitis and asthma provides further evidence that wheezy bronchitis and asthma differ in their natural history and heritability, and suggests that there may be familial factors specific to each wheezing syndrome. 



PMCID: PMC1758443  PMID: 9487342
14.  528 Elevated Asthma Prevalence in Mexican-American Children in El Paso, Texas 
The World Allergy Organization Journal  2012;5(Suppl 2):S184-S185.
Background
In the United States, among Hispanics, Mexican American have the lowest rate of asthma1,2 This study was designed to determine the prevalence of asthma among 5 to 17 year-old children, in El Paso Texas, a community area with a 65.8 % of Hispanic of origin Mexican families.
Methods
Of March 2006 to May 2010, a cross-sectional screening survey was administered to 1108 children of 751 families selected at random from 50 strata of the El Paso County. We used self-reported history of physician-diagnosed asthma. Data were analyzed to determine the prevalence of lifetime and current asthma. Associations between asthma outcomes and variable trigger were evaluated. Chi-square tests were used for statistical comparison. A P value less than 0.05 was considered to be significant. Multivariate logistic regression (GENMOD) adjusting for repeated measures for the family was used to determine the risk of childhood asthma.
Results
Self-reported physician-diagnosed asthma was reported for 25.8 % of children, and current asthma identified in 20.5 % respectively. The prevalence was statistically higher in boys than tin girls (P < 0.05). 243 (90%) Children asthmatics are atopic and 437 (51.8%) children non-asthmatics are atopic. Smoking occurred inside 23.8% of households.26.3% of children had an indoor dog or cat and 21.2% of caregivers reported cockroaches inside the home.
Conclusions
Prevalence of physician-diagnosed asthma in Hispanic of Mexican origin, ever asthma and current asthma, were higher than those reported from the Centers for Disease Control and Prevention, the prevalence of asthma in 2007. Although most children with asthma are atopic (90%) a significant proportion (51.8 %) of atopic children do not have asthma. Children with a parent with asthma were almost twice as likely (OR = 2.40) to have asthma compared those without a parent with asthma. Children with a parent and grandparent with asthma were over 4 times likely to have asthma compared to those without a parent and grandparent with asthma (OR = 4.97). Maternal asthma confers greater asthma risk to offspring than do paternal or parental asthma.
doi:10.1097/01.WOX.0000411643.26453.53
PMCID: PMC3512841
15.  Asthma and Farm Exposures in a Cohort of Rural Iowa Children 
Environmental Health Perspectives  2004;113(3):350-356.
Epidemiologic studies of farm children are of international interest because farm children are less often atopic, have less allergic disease, and often have less asthma than do nonfarm children—findings consistent with the hygiene hypothesis. We studied a cohort of rural Iowa children to determine the association between farm and other environmental risk factors with four asthma outcomes: doctor-diagnosed asthma, doctor-diagnosed asthma/medication for wheeze, current wheeze, and cough with exercise. Doctor-diagnosed asthma prevalence was 12%, but at least one of these four health outcomes was found in more than a third of the cohort. Multivariable models of the four health outcomes found independent associations between male sex (three asthma outcomes), age (three asthma outcomes), a personal history of allergies (four asthma outcomes), family history of allergic disease (two asthma outcomes), premature birth (one asthma outcome), early respiratory infection (three asthma outcomes), high-risk birth (two asthma outcomes), and farm exposure to raising swine and adding antibiotics to feed (two asthma outcomes). The high prevalence of rural childhood asthma and asthma symptoms underscores the need for asthma screening programs and improved asthma diagnosis and treatment. The high prevalence of asthma health outcomes among farm children living on farms that raise swine (44.1%, p = 0.01) and raise swine and add antibiotics to feed (55.8%, p = 0.013), despite lower rates of atopy and personal histories of allergy, suggests the need for awareness and prevention measures and more population-based studies to further assess environmental and genetic determinants of asthma among farm children.
doi:10.1289/ehp.7240
PMCID: PMC1253764  PMID: 15743727
agricultural occupational exposures; ammonia; animal feeding operations; asthma; asthma diagnosis and treatment; asthma health care policy; asthma school screening; asthma underdiagnosis; asthma undertreatment; children; chronic wheeze; cough with exercise; farming; genetic selection; hydrogen sulfide; hygiene hypothesis; odor; rural
16.  Factors associated with asthma among under-fives in Mulago hospital, Kampala Uganda: a cross sectional study 
BMC Pediatrics  2013;13:141.
Background
Asthma is the most common chronic childhood illness, with rapidly increasing prevalence in low-income countries. Among young children, asthma is often under-diagnosed.
We investigated the factors associated with asthma among under-fives presenting with acute respiratory symptoms at Mulago hospital, Uganda.
Methods
A hospital-based cross sectional study of 614 children with cough and/or difficult breathing, and fast breathing, was conducted between August 2011 and June 2012. A questionnaire focusing on clinical history of the child was administered to the caretakers. A physical examination and, laboratory and radiological investigations were done. Asthma was defined according to GINA (Global Initiative for Asthma) guidelines which were modified by excluding the symptom of “chest tightness”, spirometry/peak expiratory flow measurements and by adding chest x-ray findings to distinguish asthma from pneumonia. A panel of three paediatricians reviewed the participants’ case reports and, guided by the study definitions, made a diagnosis of asthma or other. Multivariable logistic regression analysis was done to determine factors independently associated with asthma.
Results
Of the 614 children, 128 (20.8%) had asthma, 125 (20.4%) bronchiolitis, 167 (27.2%) bacterial pneumonia only, 163 (26.5%) viral pneumonia while 31 (5.1%) had other diagnoses including pulmonary tuberculosis. The majority (71.1%) of children with asthma were aged ≥ 12 months. Factors associated with asthma included maternal asthma (AOR 2.4, 95% CI 1.2, 4.6), a history of allergy in the patient (AOR 2.6, 95% CI 1.2, 5.4,), use of gas for cooking (AOR 3.8, 95% CI 1.2, 13.3), prematurity (AOR 9.3, 95% CI 1.2, 83.3) and high level of education of caretaker (AOR 9.1, 95% CI 1.1, 72.8).
Conclusion
Maternal asthma, a history of allergy in the patient, use of gas for cooking, prematurity and high level of education of caretaker were significantly associated with asthma. There is need for studies to explore the role of the above factors in development and exacerbation of childhood asthma to provide information that can be used to design strategies for asthma prevention and control.
doi:10.1186/1471-2431-13-141
PMCID: PMC3848829  PMID: 24024970
Acute respiratory symptoms; Asthma; Associated factors; Under-five; Prevalence; Resource limited settings
17.  Is Chronic Asthma Associated with Shorter Leukocyte Telomere Length at Midlife? 
Rationale: Asthma is prospectively associated with age-related chronic diseases and mortality, suggesting the hypothesis that asthma may relate to a general, multisystem phenotype of accelerated aging.
Objectives: To test whether chronic asthma is associated with a proposed biomarker of accelerated aging, leukocyte telomere length.
Methods: Asthma was ascertained prospectively in the Dunedin Multidisciplinary Health and Development Study cohort (n = 1,037) at nine in-person assessments spanning ages 9–38 years. Leukocyte telomere length was measured at ages 26 and 38 years. Asthma was classified as life-course-persistent, childhood-onset not meeting criteria for persistence, and adolescent/adult-onset. We tested associations between asthma and leukocyte telomere length using regression models. We tested for confounding of asthma-leukocyte telomere length associations using covariate adjustment. We tested serum C-reactive protein and white blood cell counts as potential mediators of asthma-leukocyte telomere length associations.
Measurements and Main Results: Study members with life-course-persistent asthma had shorter leukocyte telomere length as compared with sex- and age-matched peers with no reported asthma. In contrast, leukocyte telomere length in study members with childhood-onset and adolescent/adult-onset asthma was not different from leukocyte telomere length in peers with no reported asthma. Adjustment for life histories of obesity and smoking did not change results. Study members with life-course-persistent asthma had elevated blood eosinophil counts. Blood eosinophil count mediated 29% of the life-course-persistent asthma-leukocyte telomere length association.
Conclusions: Life-course-persistent asthma is related to a proposed biomarker of accelerated aging, possibly via systemic eosinophilic inflammation. Life histories of asthma can inform studies of aging.
doi:10.1164/rccm.201402-0370OC
PMCID: PMC4214127  PMID: 24956257
asthma; telomere; aging; longitudinal; developmental phenotype
18.  Asthma Therapies Revisited 
Asthma is a heterogenous disorder related to numerous biologic, immunologic, and physiologic components that generate multiple clinical phenotypes. Further, genetic and environmental factors interact in ways that produce variability in both disease onset and severity and differential expression based on both the age and sex of the patient. Thus, the natural history of asthma is complex in terms of disease expression, remission, relapse, and progression. As such, therapy for asthma is complicated and has been approached from the standpoints of primary, secondary, and tertiary prevention. Presently, asthma cannot be cured but can be controlled in most patients, an indication that most of the success clinical research strategies have realized has been in the area of tertiary prevention. Since for many adult patients with asthma their disease had its roots in early life, much recent research has focused on events during early childhood that can be linked to subsequent asthma development with the hopes of creating appropriate interventions to alter its natural history of expression. These research approaches can be categorized into three questions. Who is the right patient to treat? When is the right time to begin treatment? And finally, what is the appropriate treatment to prescribe?
doi:10.1513/pats.200806-055RM
PMCID: PMC2677407  PMID: 19387036
asthma; therapy; inhaled corticosteroids; β-agonists
19.  Asthma Heredity, Cord Blood IgE and Asthma-Related Symptoms and Medication in Adulthood: A Long-Term Follow-Up in a Swedish Birth Cohort 
PLoS ONE  2013;8(6):e66777.
Cord blood IgE has previously been studied as a possible predictor of asthma and allergic diseases. Results from different studies have been contradictory, and most have focused on high-risk infants and early infancy. Few studies have followed their study population into adulthood. This study assessed whether cord blood IgE levels and a family history of asthma were associated with, and could predict, asthma medication and allergy-related respiratory symptoms in adults. A follow-up was carried out in a Swedish birth cohort comprising 1,701 consecutively born children. In all, 1,661 individuals could be linked to the Swedish Prescribed Drug Register and the Medical Birth Register, and 1,227 responded to a postal questionnaire. Cord blood IgE and family history of asthma were correlated with reported respiratory symptoms and dispensed asthma medication at 32–34 years. Elevated cord blood IgE was associated with a two- to threefold increased risk of pollen-induced respiratory symptoms and dispensed anti-inflammatory asthma medication. Similarly, a family history of asthma was associated with an increased risk of pollen-induced respiratory symptoms and anti-inflammatory medication. However, only 8% of the individuals with elevated cord blood IgE or a family history of asthma in infancy could be linked to current dispensation of anti-inflammatory asthma medication at follow-up. In all, 49 out of 60 individuals with dispensed anti-inflammatory asthma medication at 32–34 years of age had not been reported having asthma at previous check-ups of the cohort during childhood. Among those, only 5% with elevated cord blood IgE and 6% with a family history of asthma in infancy could be linked to current dispensation of anti-inflammatory asthma medication as adults. Elevated cord blood IgE and a positive family history of asthma were associated with reported respiratory symptoms and dispensed asthma medication in adulthood, but their predictive power was poor in this long-time follow-up.
doi:10.1371/journal.pone.0066777
PMCID: PMC3689672  PMID: 23805276
20.  Asthma prevalence, knowledge, and perceptions among secondary school pupils in rural and urban coastal districts in Tanzania 
BMC Public Health  2014;14:387.
Background
Asthma is a common chronic disease of childhood that is associated with significant morbidity and mortality. We aimed to estimate the prevalence of asthma among secondary school pupils in urban and rural areas of coast districts of Tanzania. The study also aimed to describe pupils’ perception towards asthma, and to assess their knowledge on symptoms, triggers, and treatment of asthma.
Methods
A total of 610 pupils from Ilala district and 619 pupils from Bagamoyo district formed the urban and rural groups, respectively. Using a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, a history of “diagnosed” asthma or the presence of a wheeze in the previous 12 months was obtained from all the studied pupils, along with documentation of their perceptions regarding asthma. Pupils without asthma or wheeze in the prior 12 months were subsequently selected and underwent a free running exercise testing. A ≥ 20% decrease in the post-exercise Peak Expiratory Flow Rate (PEFR) values was the criterion for diagnosing exercise-induced asthma.
Results
The mean age of participants was 16.8 (±1.8) years. The prevalence of wheeze in the past 12 months was 12.1% in Bagamoyo district and 23.1% in Ilala district (p < 0.001). Self-reported asthma was found in 17.6% and 6.4% of pupils in Ilala and Bagamoyo districts, respectively (p < 0.001). The prevalence of exercise-induced asthma was 2.4% in Bagamoyo, and 26.3% in Ilala (P < 0.002). In both districts, most information on asthma came from parents, and there was variation in symptoms and triggers of asthma reported by the pupils. Non-asthmatic pupils feared sleeping, playing, and eating with their asthmatic peers.
Conclusion
The prevalence rates of self-reported asthma, wheezing in the past 12 months, and exercise-induced asthma were significantly higher among urban than rural pupils. Although bronchial asthma is a common disease, pupils’ perceptions about asthma were associated with fear of contact with their asthmatic peers in both rural and urban schools.
doi:10.1186/1471-2458-14-387
PMCID: PMC4023699  PMID: 24754895
Asthma; Rural; Urban; Pupils; Tanzania
21.  292 The Relationship Between Maternal Atopy and Childhood Asthma 
Background
The diagnostic difficulty of childhood asthma leads to widespread under-diagnosis, which negatively affects the quality of life of asthmatic children. The presence of atopy in children is often used as a clinical tool to assist in making the diagnosis. However, local studies have demonstrated that atopy occurs in fewer asthmatic children than previously thought. This brings into question the association between allergy and asthma. The purpose of this study was to determine if a family history of allergy is predictive of atopic asthma in children, by comparing allergy, history of asthma and allergic symptoms, in mothers of atopic versus non-atopic asthmatic children.
Methods
A random sample of children and their mothers attending the Children's Chest and Allergy Clinic at Steve Biko Academic Hospital were enrolled. Skin-prick testing or radioallergosorbent test results, of the children were obtained from the child's hospital records. Mothers completed a detailed questionnaire which included demographic details, a history of symptoms suggestive of ‘atopy’ and allergic diseases and a history of asthma. Skin prick testing was performed on the mothers.
Results
100 children and their parents were enrolled. 64 mothers to atopic children were used as the study group and 36 mothers to non-atopic children were used as the control group. Of the 48 mothers with a positive skin prick test, 30 (64%) had atopic children (P = 0.836). Of the 16 mothers with asthma, 14 (88%) had atopic children (P = 0.045). Of the 70 mothers with a history of symptoms suggestive of an allergic disease, 45 (64%) had children with atopic asthma (P = 1.0). Of the 77 mothers who were considered to be allergic, 50 (65%) had children with atopic asthma (P = 0.806).
Conclusions
Both maternal skin prick positivity and a history of symptoms suggestive of allergic disease, are poor predictors of atopic asthma in children. This is true even in the mothers were considered to be allergic. However maternal asthma is a specific predictor of childhood atopic asthma with a good positive predictive and a high odds ratio. Further studies need to be conducted to compare the epidemiology of allergic asthma in different population groups.
doi:10.1097/01.WOX.0000412049.82446.27
PMCID: PMC3513181
22.  Asthma and Chronic Obstructive Pulmonary Disease 
Purpose of the review
In the clinical setting, patients who present with a combination of asthma and chronic obstructive pulmonary disease (COPD) related traits are not uncommon. This review discusses recent advances in the characterization of the natural course, phenotypes, and molecular markers of cases with co-existing asthma and COPD and in the understanding of the nature of the link between these two conditions.
Recent findings
Recent epidemiological evidence indicates that asthma accounts for a substantial proportion of cases of irreversible airflow limitation in the general population and that, in addition to the critical role of environmental exposures in adult age, alterations of developmental processes in childhood may also predispose subjects with asthma to COPD later in life. Findings from clinical and experimental studies emphasize the existence of remarkable heterogeneity within the group of subjects with co-existing asthma and COPD in terms of natural history of lung function, risk factors for disease progression, lung structural changes, and immunological profiles.
Summary
The phenotypic complexity of cases with co-existing asthma and COPD challenges a rigid categorization of patients into existing diagnostic labels and suggests the importance of integrating clinical, functional, morphologic, immunological, and molecular assessments to tailor and optimize prevention and treatment.
doi:10.1097/ACI.0b013e3283300baf
PMCID: PMC2832909  PMID: 19638929
asthma; chronic obstructive pulmonary disease; chronic bronchitis; emphysema
23.  Family history and the risk of early onset persistent, early onset transient and late onset asthma 
Epidemiology (Cambridge, Mass.)  2001;12(5):577-583.
Family history of asthma and allergies strongly influences asthma risk in children but the association may differ for early onset persistent, early onset transient, and late onset asthma. We analyzed the relation between family history and these types of asthma using cross-sectional data from a school-based study of 5,046 Southern California children. Parental and/or sibling history of asthma and allergy were generally more strongly associated with early onset persistent asthma compared with early onset transient or late onset asthma. For children with two asthmatic parents relative to those with none, the prevalence ratio (PR) for early onset persistent asthma was 12.1 [95% confidence interval (CI) 7.91–18.7] compared with 7.51 (95% CI 2.62–21.5) for early onset transient asthma and 5.38 (95% CI 3.40–8.50) for late onset asthma. Maternal smoking in pregnancy was predominantly related to the risk of early onset persistent asthma in the presence of parental history of allergy and asthma and the joint effects were more than additive (interaction contrast ratio = 3.10, 95% CI 1.45–4.75). Our results confirm earlier data that parental history of asthma and allergy is most strongly associated with early onset persistent asthma and suggest that among genetically predisposed children, an early life environmental exposure, maternal smoking during pregnancy, favors the development of early onset asthma that persists into later early childhood.
PMCID: PMC1618803  PMID: 11505179
asthma; wheeze; genetic susceptibility; parental; smoking; pregnancy; in utero; sibling
24.  Paternal History of Asthma and Airway Responsiveness in Children with Asthma 
Rationale: Little is known regarding the relationship between parental history of asthma and subsequent airway hyperresponsiveness (AHR) in children with asthma. Objectives: We evaluated this relationship in 1,041 children with asthma participating in a randomized trial of antiinflammatory medications (the Childhood Asthma Management Program [CAMP]). Methods: Methacholine challenge testing was performed before treatment randomization and once per year over an average of 4.5 years postrandomization. Cross-sectional and longitudinal repeated measures analyses were performed to model the relationship between PC20 (the methacholine concentration causing a 20% fall in FEV1) with maternal, paternal, and joint parental histories of asthma. Models were adjusted for potential confounders. Measurements and Main Results: At baseline, AHR was strongly associated with a paternal history of asthma. Children with a paternal history of asthma demonstrated significantly greater AHR than those without such history (median logePC20, 0.84 vs. 1.13; p = 0.006). Although maternal history of asthma was not associated with AHR, children with two parents with asthma had greater AHR than those with no parents with asthma (median logePC20, 0.52 vs. 1.17; p = 0.0008). Longitudinal multivariate analysis of the relation between paternal history of asthma and AHR using repeated PC20 measurements over 44 months postrandomization confirmed a significant association between paternal history of asthma and AHR among children in CAMP. Conclusions: Our findings suggest that the genetic contribution of the father is associated with AHR, an important determinant of disease severity among children with asthma.
doi:10.1164/rccm.200501-010OC
PMCID: PMC2718530  PMID: 15937295
airway responsiveness; asthma; genetics; longitudinal analysis; parent of origin
25.  New Insights into the Natural History of Asthma: Primary Prevention on the Horizon 
Recent studies of the natural history of asthma have shifted attention towards viral respiratory illness in early life as a major risk factor associated with the development of the most persistent forms of the disease. Although early aeroallergen sensitization is strongly associated with chronic asthma, several trials in which single aeroallergen exposure in pregnancy and early childhood was successfully accomplished and compared with sham avoidance have failed to show any decrease in asthma incidence. New evidence suggests that complex interactions occur between viral infection and aeroallergen sensitization in genetically susceptible subjects, which trigger the immune responses and airway changes that are characteristic of persistent asthma. The finding that exposure to bacterial products among children raised on farms is associated with diminished asthma prevalence during the school years has now been replicated, and experimental studies have suggested that these effects are mediated by the activation of T-regulatory cells in the airway. It is thus plausible to hypothesize that primary prevention of asthma could be attained through surrogate therapeutic interventions that activate similar mechanisms in young children at high risk for asthma.
doi:10.1016/j.jaci.2011.09.020
PMCID: PMC3963825  PMID: 22036094

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