[show abstract][hide abstract] ABSTRACT: 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. METHODS: Peripheral blood mononuclear cells from healthy control subjects (N = 93) and asthmatic children of varying disease severity (N = 66) were characterized by multi-parameter flow cytometry. RESULTS: Our findings demonstrate that children with asthma had a significantly increased frequency of Treg cells compared to children without asthma. Using a multivariate model, increased Treg cell frequency in children with asthma was most directly associated with inhaled corticosteroid use, and not asthma severity, allergic sensitization, or atopic status of the asthma. CONCLUSION: We conclude that low dose, local airway administration of corticosteroids is sufficient to impact the frequency of Treg cells in the peripheral blood. These data highlight the importance of considering medication exposure when studying Treg cells and suggest inhaled corticosteroid use in asthmatics may improve disease control through increased Treg cell frequency.
Clinical and Molecular Allergy 01/2013; 11(1):1. · 1.39 Impact Factor
[show abstract][hide abstract] ABSTRACT: Preschool rhinovirus (RV) wheezing illnesses predict an increased risk of childhood asthma; however, it is not clear how specific viral illnesses in early life relate to lung function later on in childhood.
To determine the relationship of virus-specific wheezing illnesses and lung function in a longitudinal cohort of children at risk for asthma.
Two hundred thirty-eight children were followed prospectively from birth to 8 years of age. Early life viral wheezing respiratory illnesses were assessed by using standard techniques, and lung function was assessed annually by using spirometry and impulse oscillometry. The relationships of these virus-specific wheezing illnesses and lung function were assessed by using mixed-effect linear regression.
Children with RV wheezing illness demonstrated significantly decreased spirometry values, FEV(1) (P = .001), FEV(0.5) (P < .001), FEF(25-75) (P < .001), and also had abnormal impulse oscillometry measures--more negative reactance at 5 Hz (P < .001)--compared with those who did not wheeze with RV. Children who wheezed with respiratory syncytial virus or other viral illnesses did not have any significant differences in spirometric or impulse oscillometry indices when compared with children who did not. Children diagnosed with asthma at ages 6 or 8 years had significantly decreased FEF(25-75) (P = .05) compared with children without asthma.
Among outpatient viral wheezing illnesses in early childhood, those caused by RV infections are the most significant predictors of decreased lung function up to age 8 years in a high-risk birth cohort. Whether low lung function is a cause and/or effect of RV wheezing illnesses is yet to be determined.
The Journal of allergy and clinical immunology 09/2011; 128(3):532-8.e1-10. · 9.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: In both children and adults, rhinovirus (RV) infections remain a major cause of exacerbations in asthma. With the use of both in vitro models of RV infection and experimental models of asthma exacerbation in humans, insight into the precise role of RV in this process has been obtained. RV infects the lower airways, and the virus itself, together with the immune response to the virus, leads to increased airway obstruction in some patients with asthma. Defects in the immune response to RV in these patients may also lead to increased symptom severity and to more significant exacerbations. Work further investigating the mechanisms of exacerbation caused by RV infection will ultimately lead to new modalities of treatment and possibly prevention of this common and significant cause of acute asthma.
[show abstract][hide abstract] ABSTRACT: Viral infections are important causes of asthma exacerbations in children, and lower respiratory tract infections (LRTIs), caused by viruses such as respiratory syncytial virus (RSV) and rhinovirus (RV), are a leading cause of bronchiolitis in infants. Infants hospitalized with bronchiolitis are at significantly increased risk for both recurrent wheezing and childhood asthma. To date, studies addressing the incidence of asthma after bronchiolitis severe enough to warrant hospitalization have focused almost exclusively on RSV, but a number of recent studies suggest that other respiratory pathogens, including RV, may contribute as well. It is not known whether viral bronchiolitis directly contributes to asthma causation or simply identifies infants at risk for subsequent wheezing, as from an atopic predisposition or preexisting abnormal lung function. Alternatively, the properties of the infecting virus may be important. Thus, many possible determinants exist that may contribute to the severity of bronchiolitis and the subsequent development of asthma. One such determinant is the potential involvement of genetic susceptibility loci to asthma after viral bronchiolitis, a critical area that is just beginning to be evaluated. By clarifying the roles of both host- (genetic) and virus- (environment) specific factors that contribute to the frequency and severity of viral LRTI, it may be possible to determine if severe LRTIs cause asthma, or if asthma susceptibility predisposes patients to severe LRTI in response to viral infection. Characterizing these relationships offers the potential of identifying at-risk hosts in whom preventing or delaying infection could alter the phenotypic expression of asthma.
American Journal of Respiratory and Critical Care Medicine 02/2007; 175(2):108-19. · 11.04 Impact Factor