The relationship between body fat and respiratory function in young adults.

The relationship between adiposity and respiratory function is poorly understood. Most studies investigating this have used indirect measures of body fat and few have assessed how changes in adiposity influence lung function.Body fat measured by bio-electrical impedance analysis, body mass index, waist circumference, spirometry, body plethysmography and transfer factor were measured at ages 32 and 38 years in 361 non-smoking, non-asthmatic participants from a population-based birth cohort.Higher percentage body fat was associated with lower spirometric and plethysmographic lung volumes, but not with airflow obstruction, or transfer factor at 32 years. Changes in adiposity between ages 32 and 38 years were inversely associated with changes in lung volumes. These associations were generally stronger in men than women, but an association between increasing adiposity and lower airway function (forced expiratory volume in 1 s/forced vital capacity) was only found in women. Similar associations were found for body mass index and waist circumference.Higher percentage body fat is associated with lower lung volumes. Direct and indirect measures of adiposity had similar associations with lung function. Adiposity had a greater effect on lung volumes in men than women but was associated with airway function only in women. There was little evidence that adiposity influenced transfer factor.

Accelerated decline in lung function in cigarette smokers is associated with TP53/MDM2 polymorphisms.

In vitro studies have shown that p53 mediates a protective response against DNA damage by causing either cell-cycle arrest and DNA repair, or apoptosis. These responses have not yet been demonstrated in humans. A common source of DNA damage in humans is cigarette smoke, which should activate p53 repair mechanisms. As the level of p53 is regulated by MDM2, which targets p53 for degradation, the G-allele of a polymorphism in intron 1 of MDM2 (rs2279744:G/T), that results in higher MDM2 levels, should be associated with a reduced p53 response and hence more DNA damage and corresponding tissue destruction. Similarly, the alleles of rs1042522 in TP53 that encode arginine (G-allele) or proline (C-allele) at codon 72, which cause increased pro-apoptotic (G-allele) or cell-cycle arrest activities (C-allele), respectively, may moderate p53's ability to prevent DNA damage. To test these hypotheses, we examined lung function in relation to cumulative history of smoking in a population-based cohort. The G-alleles in MDM2 and TP53 were found to be associated with accelerated smoking-related decline in lung function. These data support the hypothesis that p53 protects from DNA damage in humans and provides a potential explanation for the variation in lung function impairment amongst smokers.

Cigarette smoking and allergic sensitization: a 32-year population-based cohort study.

BACKGROUND: Cigarette smoke has immunosuppressant effects, but its effect on allergic sensitization is unclear. OBJECTIVE: To investigate associations between parental and personal smoking and skin prick tests (SPTs) for atopy in a population-based birth cohort of 1037 participants followed to adulthood. METHODS: Parental history of atopic disease, parental smoking, and personal smoking were obtained at multiple assessments between birth and age 32 years. Atopy was assessed by SPTs for 11 common inhaled allergens at ages 13 and 32 years. RESULTS: Children of atopic parents were less likely to have positive SPTs at age 13 years if either parent smoked (odds ratio, 0.55; P = .009). This association was not significant after adjusting for breast-feeding history, number of siblings, and childhood socioeconomic status. Subjects with atopic parents were also less likely to develop positive results to SPTs between ages 13 and 32 years if they smoked themselves (odds ratio, 0.18; P < .001). This reduction in risk remained significant after adjusting for multiple potential confounding factors. Neither parental nor personal smoking was significantly associated with allergic sensitization among subjects whose parents did not have a history of atopic disease. Few of those with positive SPT results at age 13 years had negative tests at age 32 years, and there was no evidence that this was influenced by smoking. CONCLUSION: Personal and parental smoking is associated with a reduced risk of allergic sensitization in people with a family history of atopy.

Systemic inflammation and lung function in young adults.

BACKGROUND: Impaired lung function is associated with systemic inflammation and is a risk factor for cardiovascular disease in older adults. It is unknown when these associations emerge and to what extent they are mediated by smoking, chronic airways disease, and/or established atherosclerosis. We explored the association between the forced expiratory volume in one second (FEV(1)) and the systemic inflammatory marker C-reactive protein (CRP) in young adults. METHODS: Associations between spirometric lung function and blood CRP were assessed in a population based birth cohort of approximately 1000 New Zealanders at ages 26 and 32 years. Analyses adjusted for height and sex to account for differences in predicted lung function and excluded pregnant women. RESULTS: There were significant inverse associations between FEV(1) and CRP at both ages. Similar results were found for the forced vital capacity. These associations were similar in men and women and were independent of smoking, asthma, and body mass index. CONCLUSIONS: Reduced lung function is associated with systemic inflammation in young adults. This association is not related to smoking, asthma, or obesity. The reasons for the association are unexplained, but the findings indicate that the association between lower lung function and increased inflammation predates the development of either chronic lung disease or clinically significant atherosclerosis. The association between poor lung function and cardiovascular disease may be mediated by an inflammatory mechanism.

Factors affecting exhaled nitric oxide measurements: the effect of sex.

BACKGROUND: Exhaled nitric oxide (F(E)NO) measurements are used as a surrogate marker for eosinophilic airway inflammation. However, many constitutional and environmental factors affect F(E)NO, making it difficult to devise reference values. Our aim was to evaluate the relative importance of factors affecting F(E)NO in a well characterised adult population. METHODS: Data were obtained from 895 members of the Dunedin Multidisciplinary Health and Development Study at age 32. The effects of sex, height, weight, lung function indices, smoking, atopy, asthma and rhinitis on F(E)NO were explored by unadjusted and adjusted linear regression analyses. RESULTS: The effect of sex on F(E)NO was both statistically and clinically significant, with F(E)NO levels approximately 25% less in females. Overall, current smoking reduced F(E)NO up to 50%, but this effect occurred predominantly in those who smoked on the day of the F(E)NO measurement. Atopy increased F(E)NO by 60%. The sex-related differences in F(E)NO remained significant (p < 0.001) after controlling for all other significant factors affecting F(E)NO. CONCLUSION: Even after adjustment, F(E)NO values are significantly different in males and females. The derivation of reference values and the interpretation of FENO in the clinical setting should be stratified by sex. Other common factors such as current smoking and atopy also require to be taken into account.

Associations between respiratory symptoms, lung function and gastro-oesophageal reflux symptoms in a population-based birth cohort.

BACKGROUND: Several studies have reported an association between asthma and gastro-oesophageal reflux, but it is unclear which condition develops first. The role of obesity in mediating this association is also unclear. We explored the associations between respiratory symptoms, lung function, and gastro-oesophageal reflux symptoms in a birth cohort of approximately 1000 individuals. METHODS: Information on respiratory symptoms, asthma, atopy, lung function and airway responsiveness was obtained at multiple assessments from childhood to adulthood in an unselected birth cohort of 1037 individuals followed to age 26. Symptoms of gastro-oesophageal reflux and irritable bowel syndrome were recorded at age 26. RESULTS: Heartburn and acid regurgitation symptoms that were at least "moderately bothersome" at age 26 were significantly associated with asthma (odds ratio = 3.2; 95% confidence interval = 1.6-6.4), wheeze (OR = 3.5; 95% CI = 1.7-7.2), and nocturnal cough (OR = 4.3; 95% CI = 2.1-8.7) independently of body mass index. In women reflux symptoms were also associated with airflow obstruction and a bronchodilator response to salbutamol. Persistent wheezing since childhood, persistence of asthma since teenage years, and airway hyperresponsiveness since age 11 were associated with a significantly increased risk of heartburn and acid regurgitation at age 26. There was no association between irritable bowel syndrome and respiratory symptoms. CONCLUSION: Reflux symptoms are associated with respiratory symptoms in young adults independently of body mass index. The mechanism of these associations remains unclear.

Leptin, adiponectin, and asthma: findings from a population-based cohort study.

BACKGROUND: Obesity is thought to increase the risk of asthma, especially in women. It has been proposed that this association could be due to the immune-modulating effect of adipokines secreted by adipose tissue. OBJECTIVE: To investigate whether aspects of the asthma phenotype are associated with higher levels of the proinflammatory adipokine leptin and lower levels of the anti-inflammatory adipokine adiponectin in a cross-sectional analysis of a group of young adults. METHODS: Associations between leptin and adiponectin and a diagnosis of asthma, symptoms of wheeze, bronchodilator response, airflow obstruction, and exhaled nitric oxide were evaluated by logistic or linear regression in a population-based birth cohort of approximately 1,000 men and women aged 32 years. Further analyses adjusted for smoking and body fat. RESULTS: There were no significant associations between leptin and any of the markers of the asthma phenotype in either men or women. In men, higher levels of adiponectin were associated with lower levels of exhaled nitric oxide but an increased risk of bronchodilator responsiveness. The inverse association with exhaled nitric oxide remained significant after adjustment for body fat, but the association with bronchodilator responsiveness did not. Adiponectin levels were not associated with any markers of asthma in women. CONCLUSIONS: The inverse association between adiponectin and exhaled nitric oxide in men warrants further investigation. However, the findings indicate that levels of leptin and adiponectin are unlikely to mediate the previously observed association between obesity and asthma.

Association between exhaled nitric oxide and systemic inflammatory markers.

BACKGROUND: Asthma is an inflammatory condition of the airways, and there is some evidence to suggest that it is associated with a systemic inflammatory response, as measured by C-reactive protein (CRP) and fibrinogen. Exhaled nitric oxide is a noninvasive measure of asthmatic airway inflammation. OBJECTIVE: To determine if there is an association between exhaled nitric oxide and these systemic inflammatory markers. METHODS: The Dunedin Multidisciplinary Health and Development Study is a birth cohort of approximately 1,000 individuals born between April 1, 1972, and March 31, 1973. At the age of 32 years, study members were assessed for diagnosis of asthma, atopy by skin prick testing, smoking, body mass index, exhaled nitric oxide, high-sensitivity serum CRP, and plasma fibrinogen level. RESULTS: There was no significant association between exhaled nitric oxide and CRP (P = .99). There was a trend to an inverse association between exhaled nitric oxide and fibrinogen (P = .049), but this was not significant after adjusting for smoking and use of corticosteroids or after further adjustment for body mass index and atopy (P = .71). CONCLUSION: In this population-based sample of young adults, there was no association between airway inflammation, as measured by exhaled nitric oxide, and systemic inflammation, as measured by either CRP or fibrinogen.

Association between exhaled nitric oxide and systemic inflammatory markers.

BACKGROUND: Asthma is an inflammatory condition of the airways, and there is some evidence to suggest that it is associated with a systemic inflammatory response, as measured by C-reactive protein (CRP) and fibrinogen. Exhaled nitric oxide is a noninvasive measure of asthmatic airway inflammation. OBJECTIVE: To determine if there is an association between exhaled nitric oxide and these systemic inflammatory markers. METHODS: The Dunedin Multidisciplinary Health and Development Study is a birth cohort of approximately 1,000 individuals born between April 1, 1972, and March 31, 1973. At the age of 32 years, study members were assessed for diagnosis of asthma, atopy by skin prick testing, smoking, body mass index, exhaled nitric oxide, high-sensitivity serum CRP, and plasma fibrinogen level. RESULTS: There was no significant association between exhaled nitric oxide and CRP (P = .99). There was a trend to an inverse association between exhaled nitric oxide and fibrinogen (P = .049), but this was not significant after adjusting for smoking and use of corticosteroids or after further adjustment for body mass index and atopy (P = .71). CONCLUSION: In this population-based sample of young adults, there was no association between airway inflammation, as measured by exhaled nitric oxide, and systemic inflammation, as measured by either CRP or fibrinogen.

Adiposity, asthma, and airway inflammation.

BACKGROUND: Several studies have found obesity to be associated with an increased prevalence of asthma. For reasons that remain unclear, this association has often been reported to be stronger in women than in men. One possible explanation might be that these studies have used body mass index to identify adiposity, which might be a less reliable measure of body fat in men than in women. OBJECTIVE: We sought to explore the association between body fat percentage measured by means of bioelectrical impedance analysis and asthma, airflow obstruction, and airway inflammation in men and women. METHODS: Respiratory questionnaires, spirometry, bronchodilator response, exhaled nitric oxide level, and percentage of body fat were measured in a population-based cohort of approximately 1000 individuals at age 32 years. RESULTS: There was a significant association between the percentage of body fat and asthma in women (P = .043) but not in men (P = .75). Airflow obstruction was associated with percentage of body fat in women (P = .046), but there was an inverse association in men (P = .010). Bronchodilator responsiveness was also associated with lower body fat in men (P = .004). Airway inflammation, measured by means of exhaled nitric oxide, was not associated with body fat in either women (P = .17) or men (P = .25). CONCLUSION: Adiposity is associated with asthma and airflow obstruction in women. This does not appear to be mediated by airway inflammation. In men airflow obstruction and bronchodilator responsiveness are associated with a lower percentage of body fat. CLINICAL IMPLICATIONS: In women, but not in men, obesity is associated with asthma and airflow obstruction, but there was no association with airway inflammation.

Sex differences in the relation between body mass index and asthma and atopy in a birth cohort.

RATIONALE: Several studies have identified an association between asthma and obesity in women. It remains unclear if this association is due to genuine asthma or to symptoms caused by overweight, at what age the association develops, and whether it is confined to females. OBJECTIVE: To explore the relations between body mass index, asthma, and atopy in a birth cohort of approximately 1,000 individuals. METHODS: Information on asthma and measurements of lung function, airway responsiveness, and atopy were obtained on multiple occasions between ages 9 and 26. Associations between these outcomes and body mass index were analyzed using generalized mixed linear regression models. Further analyses adjusted for potential covariates including breastfeeding, birth order, parental asthma, and personal and family smoking history. MAIN RESULTS: Body mass index was positively associated with asthma, wheeze, asthma treatment, atopy, immunoglobulin E, and inversely with the FEV(1)/FVC ratio in females. There was no significant association with airway responsiveness to methacholine or salbutamol. There was little evidence of an association between body mass index and asthma or atopy in males. Analyses adjusting for potential covariates showed similar findings. Asthma was not associated with a raised body mass index in childhood and childhood asthma did not lead to being overweight as an adult. CONCLUSIONS: A raised body mass index is associated with asthma and atopy in women but not men. Population attributable fraction calculations estimate that 28% (95% confidence interval 7-45) of asthma developing in women after age 9 is due to overweight.