Increasing body mass index from age 5 to 14 years predicts asthma among adolescents: evidence from a birth cohort study

Background:Obesity and asthma are common disorders, and the prevalence of both has increased in recent decades. It has been suggested that increases in the prevalence of obesity might in part explain the increase in asthma prevalence. This study aims to examine the prospective association between change in body mass index (BMI) z-score between ages 5 and 14 years and asthma symptoms at 14 years. Methods:Data was taken from the Mater University Study of Pregnancy and its outcomes (MUSP), a birth cohort of 7223 mothers and children started in Brisbane (Australia) in 1981. BMI was measured at age 5 and 14 years. Asthma was assessed from maternal reports of symptoms at age 5 and 14 years. In this study analyses were conducted on 2911 participants who had information on BMI and asthma at both ages. Results: BMI z-score at age 14 and the change in BMI z-score from age 5 to 14–years were positively associated with asthma symptoms at age 14 years, whereas BMI z-score at age 5 was not associated with asthma at age 14. Adjustment for a range of early-life exposures did not substantially alter these findings. The association between change in BMI z-score with asthma symptoms at 14 years appeared stronger for male subjects compared with female subjects but there was no statistical evidence for a sex difference (P=0.36). Conclusions: Increase in BMI z-score between age 5 and 14 years is associated with increased risk of asthma symptoms in adolescence

Achieved systolic blood pressure in older people: A systematic review and meta-analysis

Background: It remains unclear into which level the systolic blood pressure (SBP) should be lowered in order to provide the best cardiovascular protection among older people. Hypertension guidelines recommendation on attaining SBP levels 33,600 participants) were included. Compared with attaining SBP levels ≥140 mmHg, levels of 130 to <140 mmHg were not associated with lower risk of outcomes in the meta-analysis of RCTs, whereas there was an associated reduction of cardiovascular mortality (RR 0.72, 95% CI 0.59-0.88) and all-cause mortality (RR 0.86, 95% CI 0.75-0.99) in the meta-analysis of post-hoc analyses or subanalyses of RCTs. Limited and conflicting data were available for the SBP levels of <130 mmHg and 140 to <150 mmHg. Conclusions: Among older people, there is suggestive evidence that achieving SBP levels of 130 to <140 mmHg is associated with lower risks of cardiovascular and all-cause mortality. Future trials are required to confirm these findings and to provide additional evidence regarding the <130 and 140 to <150 mmHg SBP levels

Body mass index is associated with reduced exhaled nitric oxide and higher exhaled 8-isoprostanes in asthmatics

BACKGROUND: Recently, it has been shown that increasing body mass index (BMI) in asthma is associated with reduced exhaled NO. Our objective in this study was to determine if the BMI-related changes in exhaled NO differ across asthmatics and controls, and to determine if these changes are related to increased airway oxidative stress and systemic levels of leptin and adiponectin. METHODS: Observational study of the association of BMI, leptin, and adiponectin with exhaled nitric oxide (NO) and exhaled 8-isoprostanes in 67 non-smoking patients with moderate to severe persistent asthma during baseline conditions and 47 controls. Measurements included plasma levels of leptin, adiponectin, exhaled breath condensates for 8-isoprostanes, exhaled NO, pulmonary function tests, and questionnaires regarding asthma severity and control. RESULTS: In asthmatics, BMI and the ratio of leptin to adiponectin were respectively associated with reduced levels of exhaled NO (β = -0.04 [95% C.I. -0.07, -0.1], p < 0.003) and (β = -0.0018 [95% C.I. -0.003, -0.00034], p = 0.01) after adjusting for confounders. Also, BMI was associated with increased levels of exhaled 8-isoprostanes (β = 0.30 [95% C.I. 0.003, 0.6], p = 0.03) after adjusting for confounders. In contrast, we did not observe these associations in the control group of healthy non-asthmatics with a similar weight distribution. CONCLUSION: In adults with stable moderate to severe persistent asthma, but not in controls, BMI and the plasma ratio of leptin/adiponectin is associated with reduced exhaled NO. Also, BMI is associated with increased exhaled 8-isoprostanes. These results suggest that BMI in asthmatics may increase airway oxidative stress and could explain the BMI-related reductions in exhaled NO

Higher body mass index may induce asthma among adolescents with pre-asthmatic symptoms: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Limited studies have prospectively examined the role of body mass index (BMI) as a major risk factor for asthma during adolescence. This study investigates whether BMI is associated with increased risk of developing physician-diagnosed asthma during 12-month follow-up among adolescents with undiagnosed asthma-like symptoms at baseline.</p> <p>Methods</p> <p>A total of 4,052 adolescents with undiagnosed asthma-like symptoms at baseline were re-examined after a 12-month follow-up. Asthma cases were considered confirmed only after diagnosis by a physician based on the New England core and International Study of Asthma and Allergies in Childhood (ISAAC) criteria video questionnaires, and accompanying pulmonary function tests. Logistic regression analyses were used to evaluate the relationship of BMI and the risk of acquiring asthma.</p> <p>Results</p> <p>The results indicated that girls with higher BMI were at an increased risk of developing asthma during the 12-month follow-up. The odds ratios for girls developing physician-diagnosed asthma were 1.75 (95% CI = 1.18-2.61) and 1.12 (95% CI = 0.76-1.67), respectively, for overweight and obesity as compared to the normal weight reference group after adjustment for other covariates. A similar relationship was not observed for overweight and obese boys who were also significantly more active than their female counterparts.</p> <p>Conclusions</p> <p>Increased BMI exaggerates the risk of acquiring asthma in symptomatic adolescent females but not in adolescent males. Thus, gender is an important modifier of BMI-related asthma risk. Additional research will be required to determine whether the increased asthma risk results from genetic, physiological or behavioural differences.</p

Clinically diagnosed childhood asthma and follow-up of symptoms in a Swedish case control study

BACKGROUND: Childhood asthma has risen dramatically not only in the western societies and now forms a major and still increasing public health problem. The aims of this study were to follow up at the age of ten the patterns of asthma symptoms and associations among children with a clinically diagnosed asthma in a sizeable urban-rural community and to in compare them with demographic controls using a standardised questionnaire. METHODS: In a defined region in Sweden with a population of about 150 000 inhabitants, all children (n = 2 104) born in 1990 were recorded. At the age of seven all primary care and hospital records of the 1 752 children still living in the community were examined, and a group of children (n = 191) was defined with a well-documented and medically confirmed asthma diagnosis. At the age of ten, 86 % of these cases (n = 158) and controls (n = 171) completed an ISAAC questionnaire concerning asthma history, symptoms and related conditions. RESULTS: Different types of asthma symptoms were highly and significantly over-represented in the cases. Reported asthma heredity was significantly higher among the cases. No significant difference in reported allergic rhinitis or eczema as a child was found between cases and controls. No significant difference concerning social factors or environmental exposure was found between case and controls. Among the control group 4.7 % of the parents reported that their child actually had asthma. These are likely to be new asthma cases between the age of seven and ten and give an estimated asthma prevalence rate at the age of ten of 15.1 % in the studied cohort. CONCLUSION: A combination of medical verified asthma diagnosis through medical records and the use of self-reported symptom through the ISAAC questionnaire seem to be valid and reliable measures to follow-up childhood asthma in the local community. The asthma prevalence at the age of ten in the studied birth cohort is considerably higher than previous reports for Sweden. Both the high prevalence figure and allowing the three-year lag phase for further settling of events in the community point at the complementary roles of both hospital and primary care in the comprehensive coverage and control of childhood asthma in the community

Cardiovascular effects of sub-daily levels of ambient fine particles: a systematic review

<p>Abstract</p> <p>Background</p> <p>While the effects of daily fine particulate exposure (PM) have been well reviewed, the epidemiological and physiological evidence of cardiovascular effects associated to sub-daily exposures has not. We performed a theoretical model-driven systematic non-meta-analytical literature review to document the association between PM sub-daily exposures (≤6 hours) and arrhythmia, ischemia and myocardial infarction (MI) as well as the likely mechanisms by which sub-daily PM exposures might induce these acute cardiovascular effects. This review was motivated by the assessment of the risk of exposure to elevated sub-daily levels of PM during fireworks displays.</p> <p>Methods</p> <p>Medline and Elsevier's EMBase were consulted for the years 1996-2008. Search keywords covered potential cardiovascular effects, the pollutant of interest and the short duration of the exposure. Only epidemiological and experimental studies of adult humans (age > 18 yrs) published in English were reviewed. Information on design, population and PM exposure characteristics, and presence of an association with selected cardiovascular effects or physiological assessments was extracted from retrieved articles.</p> <p>Results</p> <p>Of 231 articles identified, 49 were reviewed. Of these, 17 addressed the relationship between sub-daily exposures to PM and cardiovascular effects: five assessed ST-segment depression indicating ischemia, eight assessed arrhythmia or fibrillation and five considered MI. Epidemiologic studies suggest that exposure to sub-daily levels of PM is associated with MI and ischemic events in the elderly. Epidemiological studies of sub-daily exposures suggest a plausible biological mechanism involving the autonomic nervous system while experimental studies suggest that vasomotor dysfunction may also relate to the occurrence of MI and ischemic events.</p> <p>Conclusions</p> <p>Future studies should clarify associations between cardiovascular effects of sub-daily PM exposure with PM size fraction and concurrent gaseous pollutant exposures. Experimental studies appear more promising for elucidating the physiological mechanisms, time courses and causes than epidemiological studies which employ central pollution monitors for measuring effects and for assessing their time course. Although further studies are needed to strengthen the evidence, given that exposure to sub-daily high levels of PM (for a few hours) is frequent and given the suggestive evidence that sub-daily PM exposures are associated with the occurrence of cardiovascular effects, we recommend that persons with cardiovascular diseases avoid such situations.</p

A population-based study of asthma, quality of life, and occupation among elderly Hispanic and non-Hispanic whites: a cross-sectional investigation

BACKGROUND: The U.S. population is aging and is expected to double by the year 2030. The current study evaluated the prevalence of asthma and its correlates in the elderly Hispanic and non-Hispanic white population. METHODS: Data from a sample of 3021 Hispanics and non-Hispanic White subjects, 65 years and older, interviewed as part of an ongoing cross-sectional study of the elderly in west Texas, were analyzed. The outcome variable was categorized into: no asthma (reference category), current asthma, and probable asthma. Polytomous logistic regression analysis was used to assess the relationship between the outcome variable and various socio-demographic measures, self-rated health, asthma symptoms, quality of life measures (SF-12), and various occupations. RESULTS: The estimated prevalence of current asthma and probable asthma were 6.3% (95%CI: 5.3–7.2) and 9.0% (95%CI: 7.8–10.1) respectively. The majority of subjects with current asthma (Mean SF-12 score 35.8, 95%CI: 34.2–37.4) or probable asthma (35.3, 34.0–36.6) had significantly worse physical health-related quality of life as compared to subjects without asthma (42.6, 42.1–43.1). In multiple logistic regression analyses, women had a 1.64 times greater odds of current asthma (95%CI: 1.12–2.38) as compared to men. Hay fever was a strong predictor of both current and probable asthma. The odds of current asthma were 1.78 times (95%CI: 1.24–2.55) greater among past smokers; whereas the odds of probable asthma were 2.73 times (95%CI: 1.77–4.21) greater among current smokers as compared to non-smokers. Similarly fair/poor self rated health and complaints of severe pain were independently associated with current and probable asthma. The odds of current and probable asthma were almost two fold greater for obesity. When stratified by gender, the odds were significantly greater among females (p-value for interaction term = 0.038). The odds of current asthma were significantly greater for farm-related occupations (adjusted OR = 2.09, 95%CI: 1.00–4.39); whereas the odds were significantly lower among those who reported teaching as their longest held occupation (adjusted OR = 0.36, 95%CI = 0.18–0.74). CONCLUSION: This study found that asthma is a common medical condition in the elderly and it significantly impacts quality of life and general health status. Results support adopting an integrated approach in identifying and controlling asthma in this population

Beauty Is in the Eye of the Beholder: Proteins Can Recognize Binding Sites of Homologous Proteins in More than One Way

Understanding the mechanisms of protein–protein interaction is a fundamental problem with many practical applications. The fact that different proteins can bind similar partners suggests that convergently evolved binding interfaces are reused in different complexes. A set of protein complexes composed of non-homologous domains interacting with homologous partners at equivalent binding sites was collected in 2006, offering an opportunity to investigate this point. We considered 433 pairs of protein–protein complexes from the ABAC database (AB and AC binary protein complexes sharing a homologous partner A) and analyzed the extent of physico-chemical similarity at the atomic and residue level at the protein–protein interface. Homologous partners of the complexes were superimposed using Multiprot, and similar atoms at the interface were quantified using a five class grouping scheme and a distance cut-off. We found that the number of interfacial atoms with similar properties is systematically lower in the non-homologous proteins than in the homologous ones. We assessed the significance of the similarity by bootstrapping the atomic properties at the interfaces. We found that the similarity of binding sites is very significant between homologous proteins, as expected, but generally insignificant between the non-homologous proteins that bind to homologous partners. Furthermore, evolutionarily conserved residues are not colocalized within the binding sites of non-homologous proteins. We could only identify a limited number of cases of structural mimicry at the interface, suggesting that this property is less generic than previously thought. Our results support the hypothesis that different proteins can interact with similar partners using alternate strategies, but do not support convergent evolution

Identification of KIF3A as a Novel Candidate Gene for Childhood Asthma Using RNA Expression and Population Allelic Frequencies Differences

Asthma is a chronic inflammatory disease with a strong genetic predisposition. A major challenge for candidate gene association studies in asthma is the selection of biologically relevant genes.Using epithelial RNA expression arrays, HapMap allele frequency variation, and the literature, we identified six possible candidate susceptibility genes for childhood asthma including ADCY2, DNAH5, KIF3A, PDE4B, PLAU, SPRR2B. To evaluate these genes, we compared the genotypes of 194 predominantly tagging SNPs in 790 asthmatic, allergic and non-allergic children. We found that SNPs in all six genes were nominally associated with asthma (p<0.05) in our discovery cohort and in three independent cohorts at either the SNP or gene level (p<0.05). Further, we determined that our selection approach was superior to random selection of genes either differentially expressed in asthmatics compared to controls (p = 0.0049) or selected based on the literature alone (p = 0.0049), substantiating the validity of our gene selection approach. Importantly, we observed that 7 of 9 SNPs in the KIF3A gene more than doubled the odds of asthma (OR = 2.3, p<0.0001) and increased the odds of allergic disease (OR = 1.8, p<0.008). Our data indicate that KIF3A rs7737031 (T-allele) has an asthma population attributable risk of 18.5%. The association between KIF3A rs7737031 and asthma was validated in 3 independent populations, further substantiating the validity of our gene selection approach.Our study demonstrates that KIF3A, a member of the kinesin superfamily of microtubule associated motors that are important in the transport of protein complexes within cilia, is a novel candidate gene for childhood asthma. Polymorphisms in KIF3A may in part be responsible for poor mucus and/or allergen clearance from the airways. Furthermore, our study provides a promising framework for the identification and evaluation of novel candidate susceptibility genes