Rhinoviruses A and C elicit long-lasting antibody responses with limited cross-neutralization.

Rhinoviruses (RVs) can cause severe wheezing illnesses in young children and patients with asthma. Vaccine development has been hampered by the multitude of RV types with little information about cross-neutralization. We previously showed that neutralizing antibody (nAb) responses to RV-C are detected twofold to threefold more often than those to RV-A throughout childhood.

Early life rhinovirus wheezing, allergic sensitization, and asthma risk at adolescence.

Background: Early life rhinovirus (RV) wheezing illnesses and aeroallergen sensitization increase the risk of asthma at school age. Whether these remain risk factors for the persistence of asthma out to adolescence is not established.

Objective: We sought to define the relationships among specific viral illnesses and the type and timing of aeroallergen sensitization with the persistence of asthma into adolescence.

Maternal microchimerism protects against the development of asthma.

Background: Maternal asthma and child's sex are among the most significant and reproducible risk factors for the development of asthma. Although the mechanisms for these effects are unknown, they likely involve nonclassical genetic mechanisms. One such mechanism could involve the transfer and persistence of maternal cells to her offspring, a common occurrence known as maternal microchimerism (MMc).

Inhaled corticosteroid use is associated with increased circulating T regulatory cells in children with asthma.

Background: T regulatory (Treg) cells are important in balancing immune responses and dysregulation of Treg cells has been implicated in the pathogenesis of multiple disease states including asthma. In this study, our primary aim was to determine Treg cell frequency in the peripheral blood of children with and without asthma. The secondary aim was to explore the association between Treg cell frequency with allergen sensitization, disease severity and medication use.

Protection from asthma in a high-risk birth cohort by attenuated P2X(7) function.

Background: Viral illnesses are important factors in both asthma inception and exacerbations, and allergic sensitization in early life further enhances asthma risk through unclear mechanisms. Cellular damage caused by infection or allergen inhalation increases ATP levels in the airways with subsequent purinergic receptor activation. The purinergic receptor P2X(7) can enhance airway leukocyte recruitment to the airways, and P2X(7) knockout mice display a reduced asthma-like phenotype.

Evidence for a causal relationship between allergic sensitization and rhinovirus wheezing in early life.

Rationale: Aeroallergen sensitization and virus-induced wheezing are risk factors for asthma development during early childhood, but the temporal developmental sequence between them is incompletely understood.

Objective: To define the developmental relationship between aeroallergen sensitization and virus-induced wheezing.

Methods: A total of 285 children at high risk for allergic disease and asthma were followed prospectively from birth.

IFNG genotype and sex interact to influence the risk of childhood asthma.

Background: Asthma is a complex disease characterized by sex-specific differences in incidence, prevalence, and severity, but little is known about the molecular basis of these sex-based differences.

Objective: To investigate the genetic architecture of sex differences in asthma risk, we evaluated (1) associations between polymorphisms in the IFNG gene and childhood-onset asthma in combined and sex-specific samples and (2) interactions between polymorphisms and sex on asthma risk.

Methods: Main and sex-interaction effects of IFNG genetic diversity on asthma risk and IFN-γ levels were examined in a birth cohort of children at high risk for asthma and allergic diseases.

Early childhood weight status in relation to asthma development in high-risk children.

Background: Obesity has been proposed to be a risk factor for the development of childhood asthma.

Objective: We sought to examine weight status from birth to age 5 years in relation to the occurrence of asthma at ages 6 and 8 years.

Methods: Two hundred eighty-five full-term high-risk newborns with at least 1 asthmatic/atopic parent enrolled in the Childhood Origin of Asthma project were studied from birth to age 8 years.

The relationships among immunoglobulin levels, allergic sensitization, and viral respiratory illnesses in early childhood.

IgE plays an essential role in type I allergy, however, there is less information about the relationship between other immunoglobulins (IgA and IgG) and atopic phenotypes in early childhood. We hypothesized that levels of circulating IgA in early childhood would be inversely related to the number of respiratory infections and the risk of becoming sensitized to allergens. Immunoglobulin levels were analyzed (ELISA) in plasma samples (IgG, IgA), and in nasal secretions (IgA) from children participating in a high-risk birth cohort study.

Expression patterns of atopic eczema and respiratory illnesses in a high-risk birth cohort.

Increased severity of respiratory illnesses, RSV wheezing and early allergic sensitization were significant risk factors for atopic eczema disease persistence. These children represent a distinct phenotype of AE.

Fractional exhaled nitric oxide measurements are most closely associated with allergic sensitization in school-age children.

Background: Factors affecting fractional exhaled nitric oxide (FeNO) in early childhood are incompletely understood.

Objective: To examine the relationships between FeNO and allergic sensitization, total IgE, atopic dermatitis, rhinitis, asthma, and lung function (spirometry) in children.

Methods: Children at high risk of asthma and other allergic diseases because of parental history were enrolled at birth and followed prospectively.

Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children.

Rationale: Virus-induced wheezing episodes in infancy often precede the development of asthma. Whether infections with specific viral pathogens confer differential future asthma risk is incompletely understood.

Objectives: To define the relationship between specific viral illnesses and early childhood asthma development.

Association between CD4(+)CD25(high) T cells and atopy in children.

Background: There is evidence that CD4(+)CD25(high) T-regulatory cells are important for establishing tolerance to allergens, but information in children is limited.

Objective: To test the hypothesis that greater numbers and function of CD4(+)CD25(high) T cells are associated with a reduced risk of childhood allergies and wheezing.

Methods: A cohort of 151 six-year-old children from atopic families was analyzed for peripheral blood CD4(+)CD25(high) and CD4(+)CD25(int) T cells by flow cytometry and for clinical and immunologic correlates of atopy.

Sex-related differences in immune development and the expression of atopy in early childhood.

Background: Sex and age are known to influence the clinical expression of asthma and allergic diseases.

Objective: We sought to evaluate whether immune response profiles also vary by sex and age.

Methods: We performed a prospective birth cohort study (Childhood Origins of Asthma) designed to evaluate interactions among age, sex, immune responses, and virus infections on the development of asthma and allergic diseases.

Viral infections, cytokine dysregulation and the origins of childhood asthma and allergic diseases.

Background: The origins of asthma and allergic disease begin in early life for many individuals. It is vital to understand the factors and/or events leading to their development.

Methods: The Childhood Origins of Asthma project evaluated children at high risk for asthma to study the relationships among viral infections, environmental factors, immune dysregulation, genetic factors, and the development of atopic diseases.

Rhinovirus illnesses during infancy predict subsequent childhood wheezing.

Background: The contribution of viral respiratory infections during infancy to the development of subsequent wheezing and/or allergic diseases in early childhood is not established.

Objective: To evaluate these relationships prospectively from birth to 3 years of age in 285 children genetically at high risk for developing allergic respiratory diseases.

Methods: By using nasal lavage, the relationship of timing, severity, and etiology of viral respiratory infections during infancy to wheezing in the 3rd year of life was evaluated.

Cytokine response patterns, exposure to viruses, and respiratory infections in the first year of life.

Daycare attendance and siblings are associated with viral-induced wheezing in children. Preexisting immunologic factors may influence the expression of viral infections in infancy, and in turn, recurrent infections may influence the development of immune responses. A total of 285 children were enrolled in the Childhood Origins of Asthma Project at birth and followed for at least 1 year.

Effects of dog ownership and genotype on immune development and atopy in infancy.

Background: Exposure to furred pets might confer protection against the development of allergic sensitization through a mechanism that is incompletely understood.

Objective: The objective of this study was to determine the effects of pet exposure and genotype on immunologic development and the incidence of atopic markers and diseases in the first year of life.

Methods: Pet exposure in the home was compared with cytokine secretion patterns (mitogen-stimulated mononuclear cells at birth and age 1 year) and indicators of atopy (allergen-specific and total IgE, eosinophilia, food allergy, atopic dermatitis) in 285 infants.

Developmental cytokine response profiles and the clinical and immunologic expression of atopy during the first year of life.

Background: Allergic diseases have been linked to abnormal patterns of immune development, and this has stimulated efforts to define the precise patterns of cytokine dysregulation that are associated with specific atopic phenotypes.

Objective: Cytokine-response profiles were prospectively analyzed over the first year of life and compared with the clinical and immunologic expressions of atopy.

Methods: Umbilical cord and 1-year PBMCs were obtained from 285 subjects from allergic families.