Antioxidants and air pollution in relation to indicators of asthma and COPD

Two main research questions were specified in this thesis. First, whether acute respiratory effects of air pollution can be modulated by antioxidants. Second, whether dietary or plasma antioxidants were associated with indicators of asthma and COPD.Two intervention studies investigated a possible modulation of the acute respiratory effects of ozone by antioxidant supplementation. In addition a panel study examined a possible modulation of the acute respiratory effects of winter air pollution by antioxidants in diet and serum.The first intervention study in 1994 was a pilot study among 26 cyclists who performed lung function measurements (192 observations) before and after exercise. Half of the group was randomly assigned to the supplementation group and were given a daily antioxidant supplementation of vitamins C, E andβ-carotene. The control group did not receive a placebo. We repeated the study in the summer of 1996 with a similar design but this time the study was placebo-controlled. In this study, 38 subjects (380 lung function measurements) participated until the end of the study and the antioxidant supplementation consisted of a cocktail of vitamins C and E.Both intervention studies suggest that there was an effect of ozone on FEV 1 and FVC in the control group. There was no change in lung function when ozone levels were high in the supplementation group. The difference in ozone effect between the groups for both studies was statistically significant for FEV 1 and FVC. In the analysis of the panel study, we included only subjects with chronic respiratory symptoms because these subjects showed clear acute respiratory effects of air pollution. The results suggest that subjects with low levels of plasmaβ-carotene showed an effect of air pollution on large PEF decrements, in particular, for PM10 and black smoke, whereas subjects with high levels of plasmaβ-carotene did not show an effect of air pollution. No difference in acute respiratory effects of air pollution was observed for a high versus a low dietary intake of vitamin C, E andβ-carotene or for plasmaα-tocopherol.The second research question was investigated within the MORGEN study. This study is a cross-sectional investigation on the prevalence of risk factors for chronic diseases using self-administered questionnaires and a physical examination in a randomly selected sample of the Dutch population.First, we examined the relations between dietary antioxidants (vitamins C, E andβ-carotene) and the prevalence of a number of respiratory symptoms and lung function in a population based sample of 6,555 adults. Our results suggested that a high dietary vitamin C andβ-carotene intake was associated with a higher FEV 1 and FVC. Dietary vitamin E was not associated with lung function. None of the dietary antioxidants were consistently associated with the prevalence of a number of respiratory symptoms.Second, we studied the relation between plasma levels ofβ-carotene orα-tocopherol and respiratory symptoms in a case-control sample of never and long-term former smokers. Our results suggested that cases (subjects with one or more chronic respiratory symptoms; n=491) tended to have lower plasmaβ-carotene levels than controls (n=496). Plasmaα-tocopherol was not associated with asthma and chronic bronchitis symptoms but was positively associated with dyspnea. This adverse association of plasmaα-tocopherol could not be explained by adjustment for cardiovascular risk factors and remains puzzling. Third, we evaluated the relation between plasma antioxidants (β-carotene andα-tocopherol) and lung function in a random sample (n=367) of the MORGEN study. We found that subjects with a high plasmaβ-carotene concentration tended to have a higher FVC and FEV 1 than subjects with a low plasmaβ-carotene concentration but this was not statistically significant for FEV 1 . Plasmaα-tocopherol was not associated with lung function.</p

Symptom attribution and presentation in general practice after an extreme life event

Background. A serious life event is likely to shape attributions relating to symptoms experienced afterwards. While they may play an important role in prognosis and seeking care, such perceptions have hardly been studied among survivors of a disaster. Objective. To investigate the association between self-reported health problems that have been attributed to an extreme life event and the symptoms presented to GPs. Methods. A two-wave longitudinal survey (2–3 weeks and 18 months) among survivors of a fireworks disaster was combined with a continuous morbidity surveillance in general practice. Symptoms attributed to the disaster reported in an open-ended question in the two waves were analysed using descriptive statistics. Differences in presented symptoms over time were analysed using logistic multilevel analysis. Results. More than half of the respondents reported health problems, which were, in their opinion, related to the disaster. Psychological problems were most frequently reported in association with the disaster, and in contrast to physical attributed symptoms, presentation of these problems in general practice decreased over time. In the total sample, musculoskeletal symptoms were less frequently presented in the longer term. Survivors who attributed symptoms to the disaster at both waves or after 18 months only most often presented such symptoms to the GP. Conclusion. Survivors attributed psychological problems and physical symptoms to the disaster at short-term and midterm post-disaster. Most of these survivors presented such symptoms to the GP. Attribution of symptoms to an extreme life event such as a disaster may therefore require special attention from the GP. (aut. ref

A multivariate analysis of serum nutrient levels and lung function

<p>Abstract</p> <p>Background</p> <p>There is mounting evidence that estimates of intakes of a range of dietary nutrients are related to both lung function level and rate of decline, but far less evidence on the relation between lung function and objective measures of serum levels of individual nutrients. The aim of this study was to conduct a comprehensive examination of the independent associations of a wide range of serum markers of nutritional status with lung function, measured as the one-second forced expiratory volume (FEV₁).</p> <p>Methods</p> <p>Using data from the Third National Health and Nutrition Examination Survey, a US population-based cross-sectional study, we investigated the relation between 21 serum markers of potentially relevant nutrients and FEV₁, with adjustment for potential confounding factors. Systematic approaches were used to guide the analysis.</p> <p>Results</p> <p>In a mutually adjusted model, higher serum levels of antioxidant vitamins (vitamin A, beta-cryptoxanthin, vitamin C, vitamin E), selenium, normalized calcium, chloride, and iron were independently associated with higher levels of FEV₁. Higher concentrations of potassium and sodium were associated with lower FEV₁.</p> <p>Conclusion</p> <p>Maintaining higher serum concentrations of dietary antioxidant vitamins and selenium is potentially beneficial to lung health. In addition other novel associations found in this study merit further investigation.</p

Curcumin-rich curry diet and pulmonary function in Asian older adults

10.1371/journal.pone.0051753PLoS ONE71

Selective attrition and bias in a longitudinal health survey among survivors of a disaster

BACKGROUND: Little is known about the response mechanisms among survivors of disasters. We studied the selective attrition and possible bias in a longitudinal study among survivors of a fireworks disaster. METHODS: Survivors completed a questionnaire three weeks (wave 1), 18 months (wave 2) and four years post-disaster (wave 3). Demographic characteristics, disaster-related factors and health problems at wave 1 were compared between respondents and non-respondents at the follow-up surveys. Possible bias as a result of selective response was examined by comparing prevalence estimates resulting from multiple imputation and from complete case analysis. Analysis were stratified according to ethnic background (native Dutch and immigrant survivors). RESULTS: Among both native Dutch and immigrant survivors, female survivors and survivors in the age categories 25–44 and 45–64 years old were more likely to respond to the follow-up surveys. In general, disasters exposure did not differ between respondents and non-respondents at follow-up. Response at follow-up differed between native Dutch and non-western immigrant survivors. For example, native Dutch who responded only to wave 1 reported more depressive feelings at wave 1 (59.7%; 95% CI 51.2–68.2) than Dutch survivors who responded to all three waves (45.4%; 95% CI 41.6–49.2, p < 0.05). Immigrants who responded only to wave 1 had fewer health problems three weeks post-disaster such as depressive feelings (M = 69.3%; 95% CI 60.9–77.6) and intrusions and avoidance reactions (82.7%; 95% CI 75.8–89.5) than immigrants who responded to all three waves (respectively 89.9%; 95% CI 83.4–96.9 and 96.3%; 95% CI 92.3–100, p < .01). Among Dutch survivors, the imputed prevalence estimates of wave 3 health problems tended to be higher than the complete case estimates. The imputed prevalence estimates of wave 3 health problems among immigrants were either unaffected or somewhat lower than the complete case estimates. CONCLUSION: Our results indicate that despite selective response, the complete case prevalence estimates were only somewhat biased. Future studies, both among survivors of disasters and among the general population, should not only examine selective response, but should also investigate whether selective response has biased the complete case prevalence estimates of health problems by using statistical techniques such as multiple imputation

Are physical symptoms among survivors of a disaster presented to the general practitioner? A comparison between self-reports and GP data

<p>Abstract</p> <p>Background</p> <p>Most studies examining medically unexplained symptoms (MUS) have been performed in primary or secondary care and have examined symptoms for which patients sought medical attention. Disasters are often described as precipitating factors for MUS. However, health consequences of disasters are typically measured by means of questionnaires, and it is not known whether these self-reported physical symptoms are presented to the GP. It is also not known if the self-reported symptoms are related to a medical disorder or if they remain medically unexplained. In the present study, three research questions were addressed. Firstly, were self-reported symptoms among survivors presented to the GP? Secondly, were the symptoms presented to the GP associated with a high level of functional impairment and distress? Thirdly, what was the GP's clinical judgment of the presented symptoms, i.e. were the symptoms related to a medical diagnosis or could they be labeled MUS?</p> <p>Methods</p> <p>Survivors of a man-made disaster (N = 887) completed a questionnaire 3 weeks (T1) and 18 months (T2) post-disaster. This longitudinal health survey was combined with an ongoing surveillance program of health problems registered by GPs.</p> <p>Results</p> <p>The majority of self-reported symptoms was not presented to the GP and survivors were most likely to present persistent symptoms to the GP. For example, survivors with stomachache at both T1 and T2 were more likely to report stomachache to their GP (28%) than survivors with stomachache at only T1 (6%) or only T2 (13%). Presentation of individual symptoms to the GP was not consistently associated with functional impairment and distress. 56 – 91% of symptoms were labeled as MUS after clinical examination.</p> <p>Conclusion</p> <p>These results indicate that the majority of self-reported symptoms among survivors of a disaster are not presented to the GP and that the decision to consult with a GP for an individual symptom is not dependent on the level of impairment and distress. Also, self-reported physical symptoms such as headache, back pain and shortness of breath are likely to remain medically unexplained after the clinical judgment of a GP.</p

Genetic variation in TIMP1 but not MMPs predict excess FEV1 decline in two general population-based cohorts

BACKGROUND: An imbalance in matrix metalloproteases (MMPs) and tissue inhibitors of MMPs (TIMPs) contributes to chronic obstructive pulmonary disease (COPD) development. Longitudinal studies investigating Single Nucleotide Polymorphisms (SNPs) in MMPs and TIMPs with respect to COPD development and lung function decline in the general population are lacking. METHODS: We genotyped SNPs in MMP1 (G-1607GG), MMP2 (-1306 C/T), MMP9 (3 tagging SNPs), MMP12 (A-82G and Asn357Ser) and TIMP1 (Phe124Phe and Ile158Ile) in 1390 Caucasians with multiple FEV1 measurements from a prospective cohort study in the general population. FEV1 decline was analyzed using linear mixed effect models adjusted for confounders. Analyses of the X-chromosomal TIMP1 gene were stratified according to sex. All significant associations were repeated in an independent general population cohort (n=1152). RESULTS: MMP2 -1306 TT genotype carriers had excess FEV1 decline (-4.0 ml/yr, p=0.03) compared to wild type carriers. TIMP1 Ile158Ile predicted significant excess FEV1 decline in both males and females. TIMP1 Phe124Phe predicted significant excess FEV1 decline in males only, which was replicated (p=0.10) in the second cohort. The MMP2 and TIMP1 Ile158Ile associations were not replicated. Although power was limited, we did not find associations with COPD development. CONCLUSIONS: We for the first time show that TIMP1 Phe124Phe contributes to excess FEV1 decline in two independent prospective cohorts, albeit not quite reaching conventional statistical significance in the replication cohort. SNPs in MMPs evidently do not contribute to FEV1 decline in the general population

Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma

SummaryBackgroundPrevious research has shown that diet can modify the bronchoconstrictor response to exercise in asthmatic subjects.ObjectiveDetermine the effect of ascorbic acid supplementation on pulmonary function and several urinary markers of airway inflammation in asthmatic subjects with exercise-induced bronchoconstriction (EIB).MethodsEight asthmatic subjects with documented EIB participated in a randomized, placebo controlled double-blind crossover trial. Subjects entered the study on their usual diet and were placed on either 2 weeks of ascorbic acid supplementation (1500mg/day) or placebo, followed by a 1-week washout period, before crossing over to the alternative diet. Pre- and post-exercise pulmonary function, asthma symptom scores, fraction of exhaled nitric oxide (FENO), and urinary leukotriene (LT) C4–E4 and 9α, 11β-prostagladin (PG)F2] were assessed at the beginning of the trial (usual diet) and at the end of each treatment period.Results: The ascorbic acid diet significantly reduced (p<0.05) the maximum fall in post-exercise FEV1 (−6.4±2.4%) compared to usual (−14.3±1.6%) and placebo diet (−12.9±2.4%). Asthma symptoms scores significantly improved (p<0.05) on the ascorbic acid diet compared to the placebo and usual diet. Post-exercise FENO, LTC4–E4 and 9α, 11β-PGF2 concentration was significantly lower (p<0.05) on the ascorbic acid diet compared to the placebo and usual diet.ConclusionAscorbic acid supplementation provides a protective effect against exercise-induced airway narrowing in asthmatic subjects

Level and course of FEV1 in relation to polymorphisms in NFE2L2 and KEAP1 in the general population

<p>Abstract</p> <p>Background</p> <p>The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and <it>Nfe2l2</it>-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second (FEV₁) in the general population.</p> <p>Methods</p> <p>Five <it>NFE2L2 </it>and three <it>KEAP1 </it>tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 FEV₁measurements during 3 surveys, respectively 7 FEV₁measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated FEV₁measurements.</p> <p>Results</p> <p>In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in <it>KEAP1 </it>was associated with a higher FEV₁level (p = 0.02 for an additive effect), and SNP rs2364723 in <it>NFE2L2 </it>was associated with a lower FEV₁level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of <it>KEAP1 </it>or <it>NFE2L2 </it>SNPs with FEV₁decline was observed.</p> <p>Conclusion</p> <p>This is the first genetic study on variations in key antioxidant transcriptional regulators <it>KEAP1 </it>and <it>NFE2L2 </it>and lung function in a general population. It identified 2 SNPs in <it>NFE2L2 </it>and <it>KEAP1 </it>which affect the level of FEV₁in the general population. It additionally shows that <it>NFE2L2 </it>and <it>KEAP1 </it>variations are unlikely to play a role in the longitudinal course of FEV₁in the general population.</p