Ronald E. Gangnon

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. METHODS A total of 259 children were followed prospectively from birth to 6 years of age. The etiology and timing of specific viral wheezing respiratory illnesses during early childhood were assessed using nasal lavage, culture, and multiplex reverse transcriptase-polymerase chain reaction. The relationships of these virus-specific wheezing illnesses and other risk factors to the development of asthma were analyzed. MEASUREMENTS AND MAIN RESULTS Viral etiologies were identified in 90% of wheezing illnesses. From birth to age 3 years, wheezing with respiratory syncytial virus (RSV) (odds ratio [OR], 2.6), rhinovirus (RV) (OR, 9.8), or both RV and RSV (OR , 10) was associated with increased asthma risk at age 6 years. In Year 1, both RV wheezing (OR, 2.8) and aeroallergen sensitization (OR, 3.6) independently increased asthma risk at age 6 years. By age 3 years, wheezing with RV (OR, 25.6) was more strongly associated with asthma at age 6 years than aeroallergen sensitization (OR, 3.4). Nearly 90% (26 of 30) of children who wheezed with RV in Year 3 had asthma at 6 years of age. CONCLUSIONS Among outpatient viral wheezing illnesses in infancy and early childhood, those caused by RV infections are the most significant predictors of the subsequent development of asthma at age 6 years in a high-risk birth cohort.

The Effects of Lingual Exercise on Swallowing in Older Adults

Objectives: To determine the effects of an 8‐week progressive lingual resistance exercise program on swallowing in older individuals, the most “at risk” group for dysphagia.

The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXII. The Twenty-Five-Year Progression of Retinopathy in Persons with Type 1 Diabetes

OBJECTIVE To examine the 25-year cumulative progression and regression of diabetic retinopathy (DR) and its relation to various risk factors. DESIGN Population-based study. PARTICIPANTS A total of 955 insulin-taking persons living in an 11-county area in southern Wisconsin with type 1 diabetes diagnosed before age 30 years who participated in a baseline examination (1980-1982) and at least 1 of 4 follow-up (4-, 10-, 14-, and 25-year) examinations or died before the first follow-up examination (n = 64). METHODS Stereoscopic color fundus photographs were graded using the modified Airlie House classification and the Early Treatment Diabetic Retinopathy Study retinopathy severity scheme. MAIN OUTCOME MEASURES Progression and regression of DR status. RESULTS The 25-year cumulative rate of progression of DR was 83%, progression to proliferative DR (PDR) was 42%, and improvement of DR was 18%. Progression of DR was more likely with less severe DR, male sex, higher glycosylated hemoglobin, an increase in glycosylated hemoglobin level, and an increase in diastolic blood pressure level from the baseline to the 4-year follow-up. Increased risk of incidence of PDR was associated with higher glycosylated hemoglobin, higher systolic blood pressure, proteinuria greater body mass index at baseline, and an increase in the glycosylated hemoglobin between the baseline and 4-year follow-up examinations. Lower glycosylated hemoglobin and male sex, as well as decreases in glycosylated hemoglobin and diastolic blood pressure during the first 4 years of follow-up, were associated with improvement in DR. Persons diagnosed most recently with a similar duration of diabetes had a lower prevalence of PDR independently of glycosylated hemoglobin level, blood pressure level, and presence of proteinuria. CONCLUSIONS These data show relatively high 25-year cumulative rates of progression of DR and incidence of PDR. The lower risk of prevalent PDR in more recently diagnosed persons possibly reflects improvement in care over the period of the study.

Validity of the Alcohol Use Disorders Identification Test in College Students

BACKGROUND High-risk alcohol use among college students is associated with accidents, partner violence, unwanted sexual encounters, tobacco use, and performance issues. The identification and treatment of high-risk drinking students is a priority for many college campuses and college health centers. The goal of this study was to test the psychometric properties of the Alcohol Use Disorders Identification Test (AUDIT) in college students. METHODS A convenience sample of students coming into a college health clinic was asked to complete the 10-question AUDIT and then participate in a research interview. The interview focused on assessing students for alcohol abuse and dependence by using the Composite International Diagnostic Interview Substance Abuse Module and timeline follow-back procedures to assess a 28-day drinking history. RESULTS A total of 302 students met the eligibility criteria and agreed to participate in the study. The sample consisted of 185 females (61%) and 117 males (39%), with a mean age of 20.3 years. Forty students were abstinent, 88 were high-risk drinkers, and 103 met criteria for a 12-month history of dependence. Receiver operator curves demonstrated that the AUDIT had the highest area under the cure for detecting high-risk alcohol use (0.872) and the lowest for identifying persons with a lifetime history of alcohol abuse or dependence (0.775). An AUDIT cutoff score of 6 or greater demonstrated a sensitivity of 91.0% and a specificity of 60.0% in the detection of high-risk drinkers. CONCLUSIONS The AUDIT has reasonable psychometric properties in sample of college students using student health services. This study supports the use of the AUDIT in this population.

The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXIII. The Twenty-Five-Year Incidence of Macular Edema in Persons with Type 1 Diabetes

OBJECTIVE To examine the 25-year cumulative incidence of macular edema (ME) and its relation to various risk factors. DESIGN Population-based study. PARTICIPANTS A total of 955 insulin-taking persons living in an 11-county area in southern Wisconsin with type 1 diabetes diagnosed before age 30 years who participated in baseline examinations (1980-1982) and at least 1 of 4 follow-up (4-, 10-, 14-, and 25-year) examinations (n=891) or died before the first follow-up examination (n=64). METHODS Stereoscopic color fundus photographs were graded using the modified Airlie House classification and the Early Treatment Diabetic Retinopathy Study retinopathy severity scheme. Competing risk of death was included in statistical models. MAIN OUTCOME MEASURES Incidence of ME and clinically significant ME (CSME). RESULTS The 25-year cumulative incidence was 29% for ME and 17% for CSME. Annualized incidences of ME were 2.3%, 2.1%, 2.3%, and 0.9% in the first, second, third, and fourth follow-up periods of the study, respectively. In univariate analyses, the incidence of ME was associated with male sex, more severe diabetic retinopathy, higher glycosylated hemoglobin, proteinuria, higher systolic and diastolic blood pressure, and more pack-years of smoking. Multivariate analyses showed that the incidence of ME was related to higher baseline glycosylated hemoglobin (hazard ratio [HR] per 1% 1.17; 95% confidence interval [CI], 1.10-1.25; P<0.001) and higher systolic blood pressure (HR per 10 mmHg 1.15; 95% CI, 1.04-1.26; P=0.004) and marginally to proteinuria (HR 1.43; 95% CI, 0.99-2.08; P=0.06). CONCLUSIONS These data show that relatively high 25-year cumulative rates of incidence of ME were related to glycemia and blood pressure. The lower risk of incident ME in the last period of the study may reflect recent improvement in care.

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. The timing and etiology of viral respiratory wheezing illnesses were determined, and aeroallergen sensitization was assessed annually for the first 6 years of life. The relationships between these events were assessed using a longitudinal multistate Markov model. MEASUREMENTS AND MAIN RESULTS Children who were sensitized to aeroallergens had greater risk of developing viral wheeze than nonsensitized children (hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.2-3.1). Allergic sensitization led to an increased risk of wheezing illnesses caused by human rhinovirus (HRV) but not respiratory syncytial virus. The absolute risk of sensitized children developing viral wheeze was greatest at 1 year of age; however, the relative risk was consistently increased at every age assessed. In contrast, viral wheeze did not lead to increased risk of subsequent allergic sensitization (HR, 0.76; 95% CI, 0.50-1.1). CONCLUSIONS Prospective, repeated characterization of a birth cohort demonstrated that allergic sensitization precedes HRV wheezing and that the converse is not true. This sequential relationship and the plausible mechanisms by which allergic sensitization can lead to more severe HRV-induced lower respiratory illnesses support a causal role for allergic sensitization in this developmental pathway. Therefore, therapeutics aimed at preventing allergic sensitization may modify virus-induced wheezing and the development of asthma.

Adjuvant Chemotherapy for Stage II Colon Cancer With Poor Prognostic Features

PURPOSE Adjuvant chemotherapy is typically considered for patients with stage II colon cancer characterized by poor prognostic features, including obstruction, perforation, emergent admission, T4 stage, resection of fewer than 12 lymph nodes, and poor histology. Despite frequent use, the survival advantage conferred on patients with stage II disease by chemotherapy is yet unproven. We sought to determine the overall survival benefit of chemotherapy among patients with stage II colon cancer having poor prognostic features. PATIENTS AND METHODS A total of 43,032 Medicare beneficiaries who underwent colectomy for stage II and III primary colon adenocarcinoma diagnosed from 1992 to 2005 were identified from the Surveillance, Epidemiology, and End Results (SEER) -Medicare database. χ(2) and two-way analysis of variance were used to assess differences in patient- and disease-related characteristics. Five-year overall survival was examined using Kaplan-Meier survival analysis and Cox proportional hazards regression with propensity score weighting. RESULTS Of the 24,847 patients with stage II cancer, 75% had one or more poor prognostic features. Adjuvant chemotherapy was received by 20% of patients with stage II disease and 57% of patients with stage III disease. After adjustment, 5-year survival benefit from chemotherapy was observed only for patients with stage III disease (hazard ratio[HR], 0.64; 95% CI, 0.60 to 0.67). No survival benefit was observed for patients with stage II cancer with no poor prognostic features (HR, 1.02; 95% CI, 0.84 to 1.25) or stage II cancer with any poor prognostic features (HR, 1.03; 95% CI, 0.94 to 1.13). CONCLUSION Among Medicare patients identified with stage II colon cancer, either with or without poor prognostic features, adjuvant chemotherapy did not substantially improve overall survival. This lack of benefit must be considered in treatment decisions for similar older adults with colon cancer.

Human Rhinovirus Species and Season of Infection Determine Illness Severity

RATIONALE Human rhinoviruses (HRVs) consist of approximately 160 types that cause a wide range of clinical outcomes, including asymptomatic infections, common colds, and severe lower respiratory illnesses. OBJECTIVES To identify factors that influence the severity of HRV illnesses. METHODS HRV species and types were determined in 1,445 nasal lavages that were prospectively collected from 209 infants participating in a birth cohort who had at least one HRV infection. Questionnaires were used during each illness to identify moderate to severe illnesses (MSI). MEASUREMENTS AND MAIN RESULTS Altogether, 670 HRV infections were identified, and 519 of them were solitary infections (only one HRV type). These 519 viruses belonged to 93 different types of three species: 49 A, 9 B, and 35 C types. HRV-A (odds ratio, 8.2) and HRV-C (odds ratio, 7.6) were more likely to cause MSI compared with HRV-B. In addition, HRV infections were 5- to 10-fold more likely to cause MSI in the winter months (P < 0.0001) compared with summer, in contrast to peak seasonal prevalence in spring and fall. When significant differences in host susceptibility to MSI (P = 0.004) were considered, strain-specific rates of HRV MSI ranged from less than 1% to more than 20%. CONCLUSIONS Factors related to HRV species and type, season, and host susceptibility determine the risk of more severe HRV illness in infancy. These findings suggest that anti-HRV strategies should focus on HRV-A and -C species and identify the need for additional studies to determine mechanisms for seasonal increases of HRV severity, independent of viral prevalence, in cold weather months.

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. PHA-stimulated cytokine-response profiles (IL-5, IL-10, IL-13, and IFN-gamma) were compared with blood eosinophil counts and total and specific IgE levels (dust mites, cat, egg, Alternaria species, peanut, milk, and dog) at age 1 year and at the development of atopic dermatitis and food allergy. RESULTS For the cohort as a whole, cytokine responses did not evolve according to a strict TH1 or TH2 polarization pattern. PHA-stimulated cord blood cells secreted low levels of IL-5 (2.1 pg/mL), moderate levels of IFN-gamma (57.4 pg/mL), and greater amounts of IL-13 (281.8 pg/mL). From birth to 1 year, IL-5 responses dramatically increased, whereas IL-13 and IFN-gamma responses significantly decreased. Reduced cord blood secretion of IL-10 and IFN-gamma was associated with subsequent sensitization to egg. In addition, there was evidence of TH2 polarization (increased IL-5 and IL-13 levels) associated with blood eosinophilia and increased total IgE levels by age 1 year. CONCLUSION These findings demonstrate that cytokine responses change markedly during the first year of life and provide further evidence of a close relationship between TH2 skewing of immune responses and the incidence of atopic manifestations in children.

Sedentary behavior, physical activity, and markers of health in older adults.

INTRODUCTION The purpose of this study was to examine the association between sedentary behavior (SB), cardiometabolic risk factors, and self-reported physical function by level of moderate-vigorous physical activity (MVPA). METHODS Cross-sectional analysis was completed on 1914 older adults age ≥ 65 yr from the 2003-2006 U.S. National Health and Nutrition Examination Survey. MVPA and SB were derived from ActiGraph accelerometers worn for 1 wk. MVPA was categorized as sufficient to meet the current U.S. guidelines (≥ 150 min · wk(-1)) or not; SB was split into quartiles. Various biomarkers were examined in laboratory analyses and physical exams, and the number of functional limitations was self-reported. Statistical interaction between SB and MVPA on the biomarker associations was the primary analysis, followed by an examination of their independent associations with relevant covariate adjustment. RESULTS Average SB was 9.4 ± 2.3 h · d(-1) (mean ± SD), and approximately 35% were classified as sufficiently active. Overall, no significant meaningful statistical interactions were found between SB and MVPA for any of the outcomes; however, strong independent positive associations were found between SB and weight (P < 0.01), body mass index (P < 0.01), waist circumference (P < 0.01), C-reactive protein (P < 0.01), plasma glucose (P = 0.04), and number of functional limitations (P < 0.01) after adjustment for MVPA. Similarly, MVPA was negatively associated with weight (P = 0.01), body mass index (P < 0.01), waist circumference (P < 0.01), diastolic blood pressure (P = 0.04), C-reactive protein (P < 0.01), and number of functional limitations (P < 0.01) after adjustment for SB. CONCLUSIONS The results suggest that sufficient MVPA did not ameliorate the negative associations between SB and cardiometabolic risk factors or functional limitations in the current sample and that there was independence on a multiplicative scale in their associations with the outcomes examined. Thus, older adults may benefit from the joint prescription to accumulate adequate MVPA and avoid prolonged sitting.