Small Drusen and Age-Related Macular Degeneration: The Beaver Dam Eye Study

We tested the hypothesis that large areas of small hard drusen (diameter \u3c63 μm) and intermediate drusen (diameter 63-124 μm) are associated with the incidence of age-related macular degeneration (AMD). Eyes of 3344 older adults with at least 2 consecutive visits spaced 5 years apart over a 20-year period were included. A 6-level severity scale including no drusen, 4 levels of increasing area (from minimal (\u3c2596 μm2) to large (\u3e9086 μm2)) of only small hard drusen, and intermediate drusen was used. The 5-year incidence of AMD was 3% in eyes at the start of the interval with no, minimal, small, and moderate areas of only small drusen and 5% and 25% for eyes with large area of only small drusen and intermediate drusen, respectively. Compared to eyes with a moderate area of small drusen, the odds ratio (OR) of developing AMD in eyes with a large area of only small drusen was 1.8 (p \u3c 0.001). Compared to eyes with large area of only small drusen, eyes with intermediate drusen had an OR of 5.5 (p \u3c 0.001) of developing AMD. Our results are consistent with our hypothesis that large areas of only small drusen are associated with the incidence of AMD

Detection of Pathogenic Bacteria During Rhinovirus Infection is Associated with Increased Respiratory Symptoms and Exacerbations of Asthma

Background Detection of either viral or bacterial pathogens is associated with wheezing in children, however the influence of both bacteria and virus on illness symptoms has not been described. Objective We evaluated bacterial detection during peak RV season in children with and without asthma to determine if an association exists between bacterial infection and the severity of RV illnesses. Methods 308 children (166 with asthma, 142 without asthma) ages 4–12 years provided five consecutive weekly nasal samples during September, and scored cold and asthma symptoms daily. Viral diagnostics and quantitative PCR for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were performed on all nasal samples. Results Detection rates were 53%, 17% and 11% for H. influenzae, S. pneumoniae and M. catarrhalis, respectively, with detection of RV increasing the risk of detecting bacteria within the same sample (OR 2.0, 95% CI 1.4–2.7, p<0.0001) or the following week (OR 1.6 (1.1–2.4), p=0.02). In the absence of RV, S. pneumoniae was associated with increased cold symptoms (mean 2.7 (95% CI 2.0–3.5) vs. 1.8 (1.5–2.2), p=0.006) and moderate asthma exacerbations (18% (12%–27%) vs. 9.2% (6.7%–12%), p=0.006). In the presence of RV, S. pneumoniae was associated with increased moderate asthma exacerbations (22% (16%–29%) vs. 15% (11%–20%), p=0.01). Furthermore, M. catarrhalis detected alongside RV increased the likelihood of experiencing cold and/or asthma symptoms compared to isolated detection of RV (OR 2.0 (1.0–4.1), p=0.04). Regardless of RV status, H. influenzae was not associated with respiratory symptoms. Conclusion RV infection enhances detection of specific bacterial pathogens in children with and without asthma. Furthermore, these findings suggest that M. catarrhalis and S. pneumoniae contribute to the severity of respiratory illnesses, including exacerbations of asthma

Inhaled corticosteroid use is associated with increased circulating tregulatory 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. 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

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. FeNO was measured by an online technique at ages 6 and 8 years. Relationships among FeNO, various atopic characteristics, and asthma were evaluated. Results: Reproducible FeNO measurements were obtained in 64% (135/210) of 6-year-old and 93% (180/194) of 8-year-old children. There was seasonal variability in FeNO. Children with aeroallergen sensitization at ages 6 and 8 years had increased levels of FeNO compared with those not sensitized (geometric mean; 6 years, 10.9 vs 6.7 parts per billion [ppb], P &lt; .0001; 8 years, 14.6 vs 7.1 ppb, P &lt; .0001). FeNO was higher in children with asthma than in those without asthma at 8 years but not 6 years of age (6 years, 9.2 vs 8.3 ppb, P 5 .48; 8 years, 11.5 vs 9.2 ppb, P 5 .03). At 8 years of age, this difference was no longer significant in a multivariate model that included aeroallerge

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. In addition, genetic and environmental factors that could modify risk of infections and wheezing prevalence were analyzed. Results: Risk factors for 3rd year wheezing were passive smoke exposure (odds ratio [OR] 5 2.1), older siblings (OR 5 2.5), allergic sensitization to foods at age 1 year (OR 5 2.0), any moderate to severe respiratory illness without wheezing during infancy (OR 5 3.6), and at least 1 wheezing illness with respiratory syncytial virus (RSV; OR 5 3.0), rhinovirus (OR 5 10) and/or non-rhinovirus/RSV pathogens (OR 5 3.9) during infancy. When viral etiology was considered, 1st-year wheezing illnesses caused by rhinovirus infection were the strongest predictor of subsequent 3rd year wheezing (OR 5 6.6; P &lt; .0001). Moreover, 63% of infants who wheezed during rhinovirus seasons continued to wheeze in the 3rd year of life, compared with only 20% of all other infants (OR 5 6.6; P &lt; .0001). Conclusion: In this population of children at increased risk of developing allergies and asthma, the most significant risk factor for the development of preschool childhood wheezing is the occurrence of symptomatic rhinovirus illnesses during infancy that are clinically and prognostically informative based on their seasonal nature. (J Allergy Clin Immunol 2005;116:571-7.

Enhanced Neutralizing Antibody Responses to Rhinovirus C and Age-Dependent Patterns of Infection

Knowledge of prevalent RV types, antibody responses, and populations at risk based on age and genetics may guide the development of vaccines or other novel therapies against this important respiratory pathogen.Longitudinal data from the Childhood Origins of ASThma (COAST) birth cohort study were analyzed to determine relationships between age and RV-C infections. Neutralizing antibodies specific for rhinovirus A (RV-A) and RV-C (3 types each) were determined using a novel polymerase chain reaction-based assay. We pooled data from 14 study cohorts in the United States, Finland, and Australia and used mixed-effects logistic regression to identify factors related to the proportion of RV-C versus RV-A detection.In COAST, RV-A and RV-C infections were similarly common in infancy, while RV-C was detected much less often than RV-A during both respiratory illnesses and scheduled surveillance visits (pRhinovirus C (RV-C) can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing.To identify how age and other individual-level factors are associated with susceptibility to RV-C illnesses.</div

Resolving the tail instability in weighted log-rank statistics for clustered survival data

In this note, we consider weighted log-rank statistics applied to clustered survival data with variable cluster sizes and arbitrary treatment assignments within clusters. Specifically, we verify that the contribution over the time interval for which the risk set proportion is arbitrarily small (the so-called "tail instability") is asymptotically negligible. These results were claimed but not proven by Gangnon and Kosorok [2004. Sample-size formula for clustered survival data using weighted log-rank statistics. Biometrika 91, 263-275.] who developed sample size formulas in this context. The main difficulty is that standard martingale methods cannot be used on account of the dependencies within clusters, and new methods are required.Clustered data Local alternative Log-rank statistic Martingales Multivariate survival data Tail instability