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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.

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.

Wheezing is one of the most frequent complaints that lead to the use of medical resources in younger children. Generally, wheezing is caused by bronchiolitis and resolves spontaneously without recurrence, but sometimes, wheezing can progress into asthma. Early data on the natural history of childhood wheezing was mostly obtained from retrospective reviews of medical records or from questionnaires, which made it difficult to exclude biases. Now that many cohort studies are available, reviewing the results of birth cohort studies makes it possible to understand the natural course of early childhood wheezing and the risk factors for asthma. In this study, we have reviewed the various phenotypes of early childhood wheezing and their natural courses to help select the most appropriate management modalities for the different types of early childhood wheezing.

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.

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?

Examination of intergenerational asthma beyond maternal asthma has been limited. The association between childhood asthma and intergenerational asthma status among a national cohort of children was examined.

The genealogical sample (2,552 children) participating in the Child Development Supplement of the Panel Study of Income Dynamics. Multivariate regression was used to determine intergenerational asthma.

Children with a parent with asthma were almost twice as likely (OR=1.96) to have asthma compared to those without a parent with asthma. Children with a parent and grandparent with asthma were over four times more likely to have asthma compared to those without a parent and grandparent with asthma (OR=4.27). Children with a grandparent with asthma were more likely to have asthma (OR=1.52).

A family history of asthma was a significant predictor of physician diagnosed asthma in children regardless of race/ethnicity and socioeconomic status. Findings support the collection of family history, including grandparent asthma status.

The natural history of asthma appears to be driven primarily by the timing and duration of viral respiratory infections. From the very high rate of infections in childhood, to the more sporadic pattern seen in adults, the cycle of acute injury followed by an inefficient repair process helps explain the clinical patterns of asthma severity currently recognized by asthma guidelines. Why the asthmatic host responds to viral injury in a particular way is largely a mystery and the subject of intense investigation. The role of viruses in asthma extends not just to intermittent but to persistent disease, and to both the atopic as well as nonatopic phenotypes. Future therapeutic strategies should include primary prevention via the development of antiviral innate immunity-enhancing vaccines, as well as secondary prevention via the use of antiviral agents, or immunomodulators designed to boost the antiviral response or interrupt the proinflammatory cascade.

Asthma in childhood is a heterogeneous disease with different phenotypes and variable clinical manifestations, which depend on the age, gender, genetic background, and environmental influences of the patients. Several longitudinal studies have been conducted to classify the phenotypes of childhood asthma, on the basis of the symptoms, triggers of wheezing illness, or pathophysiological features of the disease. These studies have provided us with important information about the different wheezing phenotypes in young children and about potential mechanisms and risk factors for the development of chronic asthma. The goal of these studies was to provide a better insight into the causes and natural course of childhood asthma. It is well-known that complicated interactions between genes and environmental factors contribute to the development of asthma. Because childhood is a period of rapid growth in both the lungs and the immune system, developmental factors should be considered in the pathogenesis of childhood asthma. The pulmonary system continues to grow and develop until linear growth is completed. Longitudinal studies have reported significant age-related immune development during postnatal early life. These observations suggest that the phenotypes of childhood asthma vary among children and also in an individual child over time. Improved classification of heterogeneous conditions of the disease will help determine novel strategies for primary and secondary prevention and for the development of individualized treatment for childhood asthma.

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.

Some studies have suggested that asthma may be a risk factor for coronary heart disease and stroke, particularly in women. Child and adult-onset asthma differ according to inflammatory characteristics and gender distribution. We examined whether childhood-onset and adult-onset asthma were associated with carotid artery intima-media thickness (IMT) in men and women in the Atherosclerosis Risk in Communities (ARIC) study. In unadjusted analyses, the weighted mean far wall IMT thickness for women with history of adult-onset asthma was significantly greater than that of women without history of asthma (0.731mm vs. 0.681mm; p<0.0001) while IMT for women with history of childhood-onset asthma (IMT=0.684mm) did not differ substantially from non-asthmatic women. Mean IMT did not differ significantly according to asthma history among men. When the data were fitted to a linear model, the interaction between asthma status and gender was significant (p=0.006). After adjusting for age, race, BMI, smoking status, smoking pack years, diabetes, hypertension, physical activity, education level, and high and low density lipoprotein levels, the mean IMT difference between women with adult-onset asthma and no history of asthma was attenuated but remained significant (0.713mm vs. 0.687mm, p=0.008). In conclusion, adult-onset asthma but not child-onset asthma is associated with increased carotid atherosclerosis among women but not among men.

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.

Background:

Environmental tobacco smoke (ETS) exposure is associated with poor asthma outcomes in children. However, little is known about natural changes in ETS exposure over time in children with asthma and how these changes may affect health-care utilization. This article documents the relationship between changes in ETS exposure and childhood asthma morbidity among children enrolled in a clinical trial of supervised asthma therapy.

Methods:

Data for this analysis come from a large randomized clinical trial of supervised asthma therapy in which 290 children with persistent asthma were randomized to receive either usual care or supervised asthma therapy. No smoking cessation counseling or ETS exposure education was provided to caregivers; however, children were given 20 min of asthma education, which incorporated discussion of the avoidance of asthma triggers, including ETS. Asthma morbidity and ETS exposure data were collected from caregivers via telephone interviews at baseline and at the 1-year follow-up.

Results:

At baseline, 28% of caregivers reported ETS exposure in the home and 19% reported exposure outside of the primary household only. Among children whose ETS exposure decreased from baseline, fewer hospitalizations (p = 0.034) and emergency department (ED) visits (p ≤ 0.001) were reported in the 12 months prior to the second interview compared to the 12 months prior to the first interview. Additionally, these children were 48% less likely (p = 0.042) to experience an episode of poor asthma control (EPAC).

Conclusions:

This is the first study to demonstrate an association between ETS exposure reduction and fewer EPACs, respiratory-related ED visits, and hospitalizations. These findings emphasize the importance of ETS exposure reduction as a mechanism to improve asthma control and morbidity. Potential policy implications include supporting ETS reductions and smoking cessation interventions for parents and caregivers of children with asthma. Research to identify the most cost-effective strategy is warranted.

Trial registration:

Clinicaltrials.gov Identifier: NCT00110383

Objective. Genetic heterogeneity and risk factor distribution was analyzed in two previously proposed asthma phenotypes. Method. A sample of 412 subjects was investigated at 7-8, 12-13, and 21-22 years of age with questionnaires, skin prick tests, and genetic analysis of IL-4 receptor (IL4R) single-nucleotide polymorphisms. The sample was subdivided in one group with no asthma, and two groups with asthma separated by age of onset of symptoms, namely, early onset asthma (EOA) and late onset asthma (LOA). Risk factors and IL4R markers were analyzed in respect to asthma phenotypes. Results. EOA and LOA groups were both associated with atopy and a maternal history of asthma. Female gender was more common in LOA, whereas childhood eczema, frequent colds in infancy, and a paternal history of asthma were more common in EOA. The AA genotype of rs2057768 and the GG genotype of rs1805010 were more common in LOA, whereas the GG genotype of rs2107356 was less common in EOA. Conclusion. Our data suggest that early and late onset asthma may be of different endotypes and genotypes.

Childhood asthma is not distributed evenly throughout the population, and children who grow up in crowded urban neighborhoods have higher rates of asthma and experience greater morbidity due to asthma. There are several environmental and lifestyle factors associated with urban living that are suspected to promote the development of asthma, particularly in the first few years of life. Collectively, this information suggests the hypothesis that exposure in early life to adverse environmental and lifestyle factors associated with disadvantaged urban environments modifies immune development to increase the risk for allergic diseases and asthma. The Urban Environment and Childhood Asthma birth cohort study was initiated in 2004 to test this hypothesis. The study population was recruited prenatally, and consisted of 560 families from four urban areas who were at high risk for allergies and/or asthma on the basis of parental histories, along with an additional 49 families without atopic parents. Immune development, respiratory illnesses, and exposure to stress, indoor pollutants, microbial products, and allergens were measured prospectively, and the major study outcomes are recurrent wheeze at three years of age and asthma at age seven. This review summarizes the study design, methods, and early findings of the URECA study.

Background

The objective of this study was to assess the correlation between childhood asthma and potential risk factors, especially exposure to indoor allergens, in a Native American population.

Methods

A case-control study of St. Regis Mohawk tribe children ages 2–14 years, 25 diagnosed with asthma and 25 controls was conducted. Exposure was assessed based on a personal interview and measurement of mite and cat allergens (Der p 1, Fel d 1) in indoor dust.

Results

A non-significant increased risk of childhood asthma was associated with self-reported family history of asthma, childhood environmental tobacco smoke exposure, and air pollution. There was a significant protective effect of breastfeeding against current asthma in children less than 14 years (5.2 fold lower risk). About 80% of dust mite and 15% of cat allergen samples were above the threshold values for sensitization of 2 and 1 μg/g, respectively. The association between current asthma and exposure to dust mite and cat allergens was positive but not statistically significant.

Conclusion

This research identified several potential indoor and outdoor risk factors for asthma in Mohawks homes, of which avoidance may reduce or delay the development of asthma in susceptible individuals.

The etiology and morbidity associated with asthma are thought to stem from both genetic factors and potentially modifiable environmental factors, such as viral infections.[1-7] Although it is unclear whether respiratory viral infections cause asthma, observational studies have demonstrated a high rate of asthma in children with a history of severe viral lower respiratory tract infections during infancy, and viruses are the associated with the majority of asthma exacerbations among both children and adults. This review will discuss the pathogens associated with virus-induced wheezing illnesses during infancy and early childhood, the association of bronchiolitis during infancy with an increased risk of childhood asthma, and the association of respiratory viruses with asthma exacerbations in older children and adults.

Background

Asthma is the most common chronic disease of childhood and the leading cause of childhood morbidity1. Even if an early intervention could improve their symptoms, the diagnosis of asthma in the first years of age is difficult. This study is the first effort to describe the atopic profile and the risk of developing asthma in a group of children from El Salvador with recurrent wheezing.

Methods

A questionnaire was designed for parents to determine the atopic background, while skin tests were performed in children. We used the modified Asthma Predictive Index (APIm)2 to assess the risk of developing asthma.

Results

65 children under 6 years were evaluated, with an average age of 3.5 years. The average age of onset of wheezing was at 11 months of age. Family history of asthma, chronic rhinitis and eczema were presented respectively at 25%, 19% and 8% of the population. 42% of our population presents allergic rhinitis and 37% eczema. Among the factors related to wheezing risk, we found that one third of the population was born via caesarean section with a breastfeeding average of 3.76 months; also we found the presence of pets in 26% of households, a passive smoking and exposure to wood smoke in 17% and 35% of the studied population respectively. 23 children were sensitized to respiratory allergens. Dust mites were found in 73% of children sensitized. The APIm was positive in 66% of the population.

Conclusions

This is the first cohort of children described under 6 years with recurrent wheezing in El Salvador. We found an early presentation of wheezing, caused not only by viral conditions. These children had strong personal and family atopic background with a high rate of sensitization to respiratory allergens, especially dust mites. Most of the children studied are at risk of presenting asthma in later ages.

Results from studies of traffic and childhood asthma have been inconsistent, but there has been little systematic evaluation of susceptible subgroups. In this study, we examined the relationship of local traffic-related exposure and asthma and wheeze in southern California school children (5–7 years of age). Lifetime history of doctor-diagnosed asthma and prevalent asthma and wheeze were evaluated by questionnaire. Parental history of asthma and child’s history of allergic symptoms, sex, and early-life exposure (residence at the same home since 2 years of age) were examined as susceptibility factors. Residential exposure was assessed by proximity to a major road and by modeling exposure to local traffic-related pollutants. Residence within 75 m of a major road was associated with an increased risk of lifetime asthma [odds ratio (OR) = 1.29; 95% confidence interval (CI), 1.01–1.86], prevalent asthma (OR = 1.50; 95% CI, 1.16–1.95), and wheeze (OR = 1.40; 95% CI, 1.09–1.78). Susceptibility increased in long-term residents with no parental history of asthma for lifetime asthma (OR = 1.85; 95% CI, 1.11–3.09), prevalent asthma (OR = 2.46; 95% CI, 0.48–4.09), and recent wheeze (OR = 2.74; 95% CI, 1.71–4.39). The higher risk of asthma near a major road decreased to background rates at 150–200 m from the road. In children with a parental history of asthma and in children moving to the residence after 2 years of age, there was no increased risk associated with exposure. Effect of residential proximity to roadways was also larger in girls. A similar pattern of effects was observed with traffic-modeled exposure. These results indicate that residence near a major road is associated with asthma. The reason for larger effects in those with no parental history of asthma merits further investigation.

The incidence and prognosis of childhood asthma and wheezing illness (AW) was studied using data obtained at ages 7, 11, and 16 from a national cohort of 8806 children born in 1958. By the age of 16, 24.7% were reported to have experienced at least one episode of AW. In 18.3% AW had started before the age of 8, but only 4.2% continued to have symptoms in later childhood. A further 3.6% began to have AW between the ages of 8 and 11, and 2.8% began between the ages of 12 and 16. Of those with AW at age 7, 28.3% had symptoms at 11 and 16.5% at 16; these proportions were about doubled if AW at 7 had been severe. The associations between natural history and a large number of perinatal, social, environmental, and medical factors were examined. Those which predicted the onset of AW after the age of 7 were: male sex of child; mother aged 15-19 at child's birth; history of pneumonia, whooping cough, throat or ear infections or tonsillectomy; eczema, allergic rhinitis; and periodic vomiting or abdominal pain.

Background

Asthma prevalence is lower in less developed countries and among some recent immigrant populations in the US, but the reasons for this are not clear. One possibility is that early childhood infections are protective against asthma.

Methods

We surveyed Asian immigrant children (n = 204; age 4–18) to assess the relationship between asthma and native or foreign place of birth. We included questions about environmental exposures, demographic variables and family history of asthma to test whether they might explain effects of place of birth on asthma.

Results

The native and foreign born groups were similar in most respects. Analysis of association with diagnosed asthma for all ages together resulted in two logistic regression models. Both retained born in the US (ORs were 3.2 and 4.3; p < 0.01) and family history of asthma (ORs were 6.4 and 7.2; p < 0.001). One model retained living near heavy motor traffic (OR = 2.6; p = 0.012). The other retained language (OR = 3.2; p = 0.003). However, for older children (11–18 years of age) being born in the US lost some of its predictive power.

Conclusion

Our findings are consistent with early childhood infections that are prevalent outside the US protecting against asthma.

Background

Exposure to cleaning products has frequently been reported as a symptom trigger by workers with work‐related asthma diagnosed in workers' health clinics in the city of São Paulo, Brazil.

Objectives

To estimate rhinitis and asthma symptoms prevalence and to analyse associated risk factors.

Method

A respiratory symptoms questionnaire (Medical Research Council 1976) and the International Study of Asthma and Allergies in Childhood questionnaire were applied to 341 cleaners working in the city of São Paulo, along with obtaining full occupational histories, skin prick tests and spirometry. Timing their symptoms onset in relation to occupational history allowed estimation of work‐related asthma and/or rhinitis. Risk factors related to selected outcomes were analysed by logistic regression.

Results

11% and 35% of the cleaners had asthma and rhinitis, respectively. The risk of work‐related asthma/rhinitis increased with years of employment in non‐domestic cleaning (OR 1.09, 95% CI 1.00 to 1.18, >0.92–3 years; OR 1.28, 95% CI 1.01 to 1.63, >3–6.5 years; OR 1.71, 95% CI 1.02 to 2.89, >6.5 years). Atopy was associated with asthma and rhinitis (OR 2.91, 95% CI 1.36 to 6.71; OR 2.06, 95% CI 1.28 to 3.35, respectively). There was a higher risk of rhinitis in women (OR 2.07, 95% CI 1.20 to 3.70).

Conclusions

Cleaning workers are at risk of contracting work‐related asthma and/or rhinitis, and the risk increases with years of employment in non‐domestic cleaning. Women present higher risk of rhinitis than men.

In developing these international guidelines there were several unifying themes in the diagnosis and simple management of childhood asthma. For the purposes of the meeting, asthma was operationally defined as 'episodic wheeze and/or cough in a clinical setting where asthma is likely and other rarer conditions have been excluded'. In making a diagnosis of asthma, a full history is a prerequisite. Additional tests are only used to support clinical impression and to provide objective evidence for therapeutic recommendations. General features of a multidisciplinary approach include an appreciation of the importance of psychosocial factors, counselling, and education. Drugs should be prescribed in a rational sequence: beta 2-stimulants for mild episodic wheeze; sodium cromoglycate for mild to moderate asthma; inhaled steroids for moderate to severe asthma; with xanthines, ipratropium bromide, and oral steroids having their place in more persistent and severe cases. Children and their parents should be reassured that if asthma is properly controlled there is no reason why the child should not lead a normal and physically active life. The management of asthma is rewarding and return to 'normal' lifestyle is nearly always possible with active participation in sporting activities.

Images

We report the first complete population based study of childhood deaths due to asthma. All deaths ascribed to asthma in New Zealand children aged 0-14 were investigated as part of a two year national study of mortality from asthma. The 16 children who died from asthma all developed asthma by the age of 4; 15 had a family history of asthma, and 12 had associated atopic disorders. Disturbed pyschosocial relationships were evident in eight families. Seven children died in less than three hours from the onset of their final attack. All children died outside hospital. Mortality from asthma in Maori children (3.14 per 100 000) was five times that of European children. With hindsight, factors which if avoided could have led to a different outcome were identified in eleven cases. The circumstances surrounding these deaths were similar to those described for adults with asthma; this study, however, underlines the importance of parental care and knowledge in the management of children with asthma. Inadequate long term medical care, underassessment of severity by family and doctors, failure of the family to call for help when required, and inadequate responses of medical services contributed to the fatalities. Excess beta2 sympathomimetic dosage or overreliance on home nebulisers were uncommon. Most childhood deaths from asthma should be prevented by increased family awareness, better assessment of severity, improved long term treatment, and rapid access to emergency medical care.

Background

The incidence and morbidity of wheezing illnesses and childhood asthma is especially high in poor urban areas. This paper describes the study design, methods, and population of the Urban Environment and Childhood Asthma (URECA) study, which was established to investigate the immunologic causes of asthma among inner-city children.

Methods and Results

URECA is an observational prospective study that enrolled pregnant women in central urban areas of Baltimore, Boston, New York City, and St. Louis and is following their offspring from birth through age 7 years. The birth cohort consists of 560 inner-city children who have at least one parent with an allergic disease or asthma, and all families live in areas in which at least 20% of the population has incomes below the poverty line. In addition, 49 inner-city children with no parental history of allergies or asthma were enrolled. The primary hypothesis is that specific urban exposures in early life promote a unique pattern of immune development (impaired antiviral and increased Th2 responses) that increases the risk of recurrent wheezing and allergic sensitization in early childhood, and of asthma by age 7 years. To track immune development, cytokine responses of blood mononuclear cells stimulated ex vivo are measured at birth and then annually. Environmental assessments include allergen and endotoxin levels in house dust, pre- and postnatal maternal stress, and indoor air nicotine and nitrogen dioxide. Nasal mucous samples are collected from the children during respiratory illnesses and analyzed for respiratory viruses. The complex interactions between environmental exposures and immune development will be assessed with respect to recurrent wheeze at age 3 years and asthma at age 7 years.

Conclusion

The overall goal of the URECA study is to develop a better understanding of how specific urban exposures affect immune development to promote wheezing illnesses and asthma.

Summary

Viral infections affect wheezing and asthma in children and adults of all ages. In infancy, wheezing illnesses are usually viral in origin, and children with more severe wheezing episodes are more likely to develop recurrent episodes of asthma and to develop asthma later in childhood. Children who develop allergen-specific immunoglobulin E (allergic sensitization), and those who wheeze with rhinoviruses (HRV) are at especially high risk for asthma. In older children and adults, HRV infections generally cause relatively mild respiratory illnesses and yet contribute to acute and potentially severe exacerbations in patients with asthma. These findings underline the importance of understanding the synergistic nature of allergic sensitization and infections with HRV in infants relative to the onset of asthma and in children and adults with respect to exacerbations of asthma. This review discusses clinical and experimental evidence of virus/allergen interactions and evaluates theories which relate immunologic responses to respiratory viruses and allergens to the pathogenesis and disease activity of asthma. Greater understanding of the relationship between viral respiratory infections, allergic inflammation, and asthma is likely to suggest new strategies for the prevention and treatment of asthma.