Reduction of exercise‐induced asthma oxidative stress by lycopene, a natural antioxidant Lack of acute effects of ascorbic acid on spirometry and airway responsiveness to histamine in subjects with asthma. Antioxidant supplementation and nasal inflammatory responses among young asthmatics exposed to high levels of ozone Effects of magnesium supplementation on the glutathione redox system in atopic asthmatic children Manipulating antioxidant intake in asthma: a randomized controlled trial. MicroRNA Expression in Response to Controlled Exposure to Diesel Exhaust: Attenuation by the Antioxidant N-Acetylcysteine in a Randomized Crossover Study Respiratory outcomes in early childhood following antenatal vitamin C and E supplementation Changes in levels of catalase and glutathione in erythrocytes of patients with stable asthma, treated with beclomethasone dipropionate. Randomised, double blind, placebo-controlled trial of selenium supplementation in adult asthma Pycnogenol((R)) in the Management of Asthma. The effect of sulphurous air pollutant exposures on symptoms, lung function, exhaled nitric oxide, and nasal epithelial lining fluid antioxidant concentrations in normal and asthmatic adults Randomised aspirin assignment and risk of adult-onset asthma in the Women’s Health Study DASH for asthma: a pilot study of the DASH diet in not-well-controlled adult asthma. Blocking effect of vitamin C in exercise-induced asthma. Exhaled carbon monoxide levels in atopic asthma: a longitudinal study. Antioxidants and asthma: will the patient benefit? [Editorial]. What are minimal important changes for asthma measures in a clinical trial? Impact of Adjunctive Therapy with Chlorellav ulgaris Extract on Antioxidant Status, Pulmonary Function, and Clinical Symptoms of Patients with Obstructive Pulmonary Diseases Randomized trial of the effect of an integrative medicine approach to the management of asthma in adults on disease-related quality of life and pulmonary function. Managed-Medicare Health Club Benefit and Reduced Health Care Costs Among Older Adults Effects of N-acetylcysteine on asthma exacerbation. Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma. Lycopene-rich treatments modify noneosinophilic airway inflammation in asthma: Proof of concept Genetic polymorphism of GSTM1 and antioxidant supplementation influence lung function in relation to ozone exposure in asthmatic children in Mexico City. A novel dietary intervention to optimize vitamin E intake of pregnant women to 15 mg/day. Lack of systemic oxidative stress during PAF challenge in mild asthma. Asthma, chronic obstructive pulmonary disease, and type 2 diabetes in the Women's Health Study. Oral magnesium and vitamin C supplements in asthma: a parallel group randomized placebo‐controlled trial Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants. Dietary Intake of Soy Genistein is Associated with Lung Function in Patients with Asthma Lycopene and the Lung The effect of vitamin C on antigen-induced bronchospasm. Effects of selenium supplementation on expression of adhesion molecules in corticoid-dependent asthmatics. Estradiol in premenstrual asthma: a double-blind, randomized, placebo-controlled, crossover study. Pycnogenol® as an Adjunct in the Management of Childhood Asthma Dietary Antioxidants and Ozone-Induced Bronchial Hyperresponsiveness in Adults with Asthma [Aevit and glutamic acid in the treatment of patients with bronchial asthma]. Flow cytometry to identify leukocyte sub-populations in blood and induced sputum in asthmatic and healthy volunteers exposed to diesel exhaust Vitamin E supplements in asthma: a parallel group randomised placebo controlled trial High dose ascorbic acid in Nigerian asthmatics. Ascorbic acid in bronchial asthma. Effects of cysteine donor supplementation on exercise-induced bronchoconstriction. Antiinflammatory-antioxidant treatment with a methane sulfonanilide in allergen-induced asthma. Active and passive smoking and risk of colds in women. [Clinical and biochemical aspects of flixotide administration in patients with moderate bronchial asthma]. Nutritional supplement therapy improves oxidative stress, immune response, pulmonary function, and quality of life in allergic asthma patients: an open-label pilot study. The attenuation of exercise-induced bronchospasm by ascorbic acid. The effects of add-on zafirlukast treatment to budesonide on bronchial hyperresponsiveness and serum levels of eosinophilic cationic protein and total antioxidant capacity in asthmatic patients. Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial. Effects of Supportive Treatment such as Antioxidant or Leukotriene Receptor Antagonist Drugs on Inflammatory and Respiratory Parameters in Asthma Patients Effect of lycopene supplementation on lung function after exercise in young athletes who complain of exercise-induced bronchoconstriction symptoms. Effect of Inhaled Glutathione on Airway Response to ‘Fog’ Challenge in Asthmatic Patients Corticosteroid sparing effects of vitamin C and magnesium in asthma: a randomised trial. Glutathione in induced sputum of healthy individuals and patients with asthma Effect of apocynin on ozone-induced airway hyperresponsiveness to methacholine in asthmatics. [The antioxidative-prooxidative balance in children with asthma treated with inhaled corticosteroids and long acting beta2-agonists]. Relation between theophylline and circulating vitamin levels in children with asthma.
Background : Lycopene has previously been shown to have high antioxidative activity . In view of the controversy regarding the beneficial effect of antioxidants on asthma , the acute effects  of lycopene ( LYC‐O‐MATOTM )  on airway hyperreactivity were assessed in patients with exercise‐induced asthma ( EIA ) Sixteen adult subjects with asthma in a clinical steady state were studied . On day 1 , after baseline spirometry , they underwent four histamine inhalation tests with functional recovery between each test . The provocative concentration causing a 20 % fall in FEV1 ( PC20 ) was obtained after each test . On days 2 , 3 , and 4 , after baseline spirometry , active and placebo ascorbic acid ( 2 gm ) was administered orally , double-blind , according to a 4.3.1 two-treatment crossover study design . One hour later , spirometry was performed , and PC20 was reassessed . We found no significant changes in FEV1 and FVC after ascorbic acid as compared with placebo administration . There was no difference between PC20 on days 2 , 3 , and 4 and by st and ardizing for the four PC20 results obtained on day 1 . We conclude that ascorbic acid has no acute bronchodilator effect and does not alter bronchial responsiveness to histamine in subjects with asthma The inflammatory response to ozone in atopic asthma suggests that soluble mediators of inflammation are released in response to oxidant stress . Antioxidants may alleviate additional oxidative stress associated with photochemical oxidant pollution . This study investigates the impact of antioxidant supplementation on the nasal inflammatory response to ozone exposure in atopic asthmatic children . We conducted a r and omized trial using a double‐blinded design . Children with asthma ( n = 117 ) , residents of Mexico City , were given r and omly a daily supplement of vitamins ( 50 mg/day of vitamin E and 250 mg/day of vitamin C ) or placebo . Nasal lavages were performed three times during the 4‐month follow‐up and analysed for content of interleukin‐6 ( IL‐6 ) , IL‐8 , uric acid and glutathione ( GSx ) . IL‐6 levels in the nasal lavage were increased significantly in the placebo group after ozone exposure while no increase was observed in the supplement group . The difference in response to ozone exposure between the two groups was significant ( P = 0·02 ) . Results were similar for IL‐8 , but with no significant difference between the groups ( P = 0·12 ) . GSx decreased significantly in both groups . Uric acid decreased slightly in the placebo group . Our data suggest that vitamin C and E supplementation above the minimum dietary requirement in asthmatic children with a low intake of vitamin E might provide some protection against the nasal acute inflammatory response to ozone Abstract . Objective : Our aim was to investigate the effects of 12-week oral magnesium ( Mg ) supplementation on the RBC redox system in stable , persistent , moderately asthmatic children ( N = 40 , 24 boys , 16 girls ) aged 4–16 years in a r and omized , double-blind , placebo-controlled study . Design : Oxidized ( GSSG ) and reduced ( GSH ) glutathione , oxyhaemoglobin , methaemoglobin ( metHb ) , hemichrome and bilirubin levels before and after treatment were determined , and GSH stability tests were performed . Result : The GSH concentration was significantly higher in the Mg-treated than in the placebo-treated patients after the treatment period . There was a positive correlation between the decreased plasma metHb and hemichrome levels and the decreased plasma haemoglobin concentrations in the Mg-treated patients at the end of the study . Conclusion : Mg in the given doses exerts antioxidant activity and influences the glutathione redox system BACKGROUND Antioxidant-rich diets are associated with reduced asthma prevalence in epidemiologic studies . We previously showed that short-term manipulation of antioxidant defenses leads to changes in asthma outcomes . OBJECTIVE The objective was to investigate the effects of a high-antioxidant diet compared with those of a low-antioxidant diet , with or without lycopene supplementation , in asthma . DESIGN Asthmatic adults ( n = 137 ) were r and omly assigned to a high-antioxidant diet ( 5 servings of vegetables and 2 servings of fruit daily ; n = 46 ) or a low-antioxidant diet ( ≤2 servings of vegetables and 1 serving of fruit daily ; n = 91 ) for 14 d and then commenced a parallel , r and omized , controlled supplementation trial . Subjects who consumed the high-antioxidant diet received placebo . Subjects who consumed the low-antioxidant diet received placebo or tomato extract ( 45 mg lycopene/d ) . The intervention continued until week 14 or until an exacerbation occurred . RESULTS After 14 d , subjects consuming the low-antioxidant diet had a lower percentage predicted forced expiratory volume in 1 s and percentage predicted forced vital capacity than did those consuming the high-antioxidant diet . Subjects in the low-antioxidant diet group had increased plasma C-reactive protein at week 14 . At the end of the trial , time to exacerbation was greater in the high-antioxidant than in the low-antioxidant diet group , and the low-antioxidant diet group was 2.26 ( 95 % CI : 1.04 , 4.91 ; P = 0.039 ) times as likely to exacerbate . Of the subjects in the low-antioxidant diet group , no difference in airway or systemic inflammation or clinical outcomes was observed between the groups that consumed the tomato extract and those who consumed placebo . CONCLUSIONS Modifying the dietary intake of carotenoids alters clinical asthma outcomes . Improvements were evident only after increased fruit and vegetable intake , which suggests that whole-food interventions are most effective . This trial was registered at http://www.actr.org.au as ACTRN012606000286549 Background : Adverse health effects associated with diesel exhaust ( DE ) are thought to be mediated in part by oxidative stress , but the detailed mechanisms are largely unknown . MicroRNAs ( miRNAs ) regulate gene expression post-transcriptionally and may respond to exposures such as DE . Objectives : We profiled peripheral blood cellular miRNAs in participants with mild asthma who were exposed to controlled DE with and without antioxidant supplementation .  Methods : Thirteen participants with asthma underwent controlled inhalation of filtered air and DE in a double-blinded , r and omized crossover study of three conditions : a ) DE plus placebo ( DEP ) , b ) filtered air plus placebo ( FAP ) , or c ) DE with N-acetylcysteine supplementation ( DEN ) . Total cellular RNA was extracted from blood drawn before exposure and 6 hr after exposure for miRNA profiling by the NanoString nCounter assay . MiRNAs significantly associated with DEP exposure and a predicted target [ nuclear factor ( erythroid-derived 2)-like 2 ( NRF2 ) ] as well as antioxidant enzyme genes were assessed by reverse transcription – quantitative polymerase chain reaction ( RT-qPCR ) for validation , and we also assessed the ability of N-acetylcysteine supplementation to block the effect of DE on these specific miRNAs . 8-hydroxy-2´-deoxyguanosine ( 8-OHdG ) was measured in plasma as a systemic oxidative stress marker . Results : Expression of miR-21 , miR-30e , miR-215 , and miR-144 was significantly associated with DEP . The change in miR-144 was vali date d by RT-qPCR . NRF2 and its downstream antioxidant genes [ glutamate cysteine ligase catalytic subunit ( GCLC ) and NAD(P)H : quinone oxidoreductase 1 ( NQO1 ) ] were negatively associated with miR-144 levels . Increases in miR-144 and miR-21 were associated with plasma 8-hydroxydeoxyguanosine 8-OHdG level and were blunted by antioxidant ( i.e , DEN ) . Conclusions : Systemic miRNAs with plausible biological function are altered by acute moderate-dose DE exposure . Oxidative stress appears to mediate DE-associated changes in miR-144 Background Prenatal antioxidant supplementation might influence fetal lung growth and development and reduce infant respiratory morbidity . The aim of this study was to test the hypothesis that infants of mothers at risk of pre-eclampsia who were r and omised to receive high-dose vitamins C and E ( 1000 mg vitamin C and 400 IU RRR α-tocopherol daily ) during pregnancy would have better respiratory outcomes than infants whose mothers were r and omised to receive placebo . Methods Respiratory outcomes to 2 years of age were documented using question naires and , in a subset , by recording their healthcare utilisation and calculating the cost of care data . Results 330 women who had taken vitamin supplementation and 313 who had taken placebo completed the respiratory question naire ( 386 and 366 infants , respectively ) . There were no significant differences between the two groups in the proportions diagnosed with asthma . 54 women who had taken vitamin supplementation and 45 who had taken placebo  took part in the healthcare utilisation study ( 65 and 53 infants , respectively ) . On average , infants of mothers receiving vitamin supplementation had 2.6 ( 99 % CI 0.8 to 5.1 ) times more A&E/outpatient visits and 3.2 ( 99 % CI 0.2 to 6.9 ) times more GP visits than infants of mothers receiving placebo , and their costs of care were £ 226 ( 99 % CI £ 27 to £ 488 ) more for outpatient admissions , £ 57 ( 99 % CI £ 3 to £ 123 ) more for GP visits and £ 22 ( 99 % CI £ 3 to £ 50 ) more for medications . Conclusions High-dose antenatal vitamin C and E supplementation  does not improve infant respiratory outcome and is associated with increased healthcare utilisation and cost of care In asthmatic patients , antioxidant defence is decreased . Although inhaled corticosteroids decrease asthmatic inflammation and modulate reactive oxygen species ( ROS ) generation , little is known of their effect on cellular antioxidant levels . The aim of this study was to evaluate the effect of inhaled beclomethasone dipropionate ( BDP ; 1,000 microg x day(-1 ) ) on erythrocyte antioxidant levels in stable asthmatic patients . Forty patients with stable , mild asthma were treated in a double-blind , placebo-controlled , parallel-group study with BDP 250 microg , two puffs b.i.d . for 6 weeks . At entry and every 2 weeks during treatment , erythrocyte antioxidant levels , haematological parameters , pulmonary function tests and asthma symptoms were determined . The results show that during treatment with BDP , erythrocyte catalase levels increased ( at entry ( mean + /-SEM ) 41+/-4 , after 6 weeks 54+/-4 micromol H2O2 x min(-1 ) x g haemoglobin (Hb)(-1 ) , p = 0.05 in comparison with placebo ) . Erythrocyte total glutathione levels significantly decreased after 6 weeks treatment with BDP ( from 7.0+/-0.4 to 6.6+/-0.3 micromol x g Hb(-1 ) ( p = 0.04 ) ) . In the BDP-treated patients , blood eosinophil counts were higher in patients who responded with an increase in erythrocyte catalase levels during BDP treatment , as compared to those not responding ( ( mean + /-SEM ) 340+/-39 and 153+/-52x10(6 ) cells x L(-1 ) , respectively , p = 0.05 ) . The present study shows that treatment with inhaled bedomethasone dipropionate results in changes in antioxidant levels in erythrocytes of patients with stable , mild asthma Background : Epidemiological evidence from observational studies has suggested that blood levels and dietary intake of selenium of adults with asthma are lower than those of controls . The only previous trial of selenium supplementation in adults with asthma found no objective evidence of benefit but involved only 24 participants . Methods : A r and omised , double blind , placebo-controlled trial of selenium supplementation was performed in adults with asthma in London , UK , the majority of whom ( 75 % ) reported inhaled steroid use at baseline . 197 participants were r and omised to receive either a high-selenium yeast preparation ( 100 µg daily , n = 99 ) or placebo ( yeast only , n = 98 ) for 24 weeks . The primary outcome was asthma-related quality of life ( QoL ) score . Secondary outcomes included lung function , asthma symptom scores , peak flow and bronchodilator usage . Linear regression was used to analyse the change in outcome between the two treatment arms by “ intention to treat ” . Results : There was a 48 % increase in plasma selenium between baseline and end of trial in the active treatment group but no change in the placebo group . While the QoL score improved more in the active treatment group than in the placebo group , the difference in change in score between the two groups was not significant ( −0.05 ( 95 % CI −0.19 to 0.09 ) ; p = 0.47 ) . Selenium supplementation was not associated with any significant improvement in secondary outcomes compared with placebo . Conclusions : Selenium supplementation had no clinical benefit in adults with asthma , the majority of whom were taking inhaled steroids Asthma is characterized as a chronic inflammatory process . Pycnogenol((R ) ) , a bioflavonoid mixture extracted from Pinus maritima , is known to scavenge free radicals while possessing antioxidant and antiinflammatory properties . The objective of this study was to evaluate the efficiency of this agent in a r and omized , double-blinded , placebo-controlled , crossover study in patients with varying asthma severity . Twenty-six patients who fulfilled the American Thoracic Society criteria for asthma were enrolled in the study . Medical history , physical examination , blood sample analyses , and spirometric values were obtained at baseline , 4 weeks , and 8 weeks . The patients were r and omly assigned to receive either 1 mg/lb/day ( maximum 200 mg/day ) Pycnogenol or placebo for the first period of 4 weeks and then crossed over to the alternate regimen for the next 4 weeks . No adverse effects were observed related to the study drug . Within the contingent of 22 patients who completed the study , almost all responded favorably to Pycnogenol in contrast to placebo . Pycnogenol treatment also significantly reduced serum leukotrienes compared with placebo . The results of this pilot study indicate that Pycnogenol may be a valuable nutraceutical in the management of chronic asthma . We recommend that further clinical trials be conducted in larger groups of asthmatics to establish its efficacy Aims : To explore the effects in normal and asthmatic adults of exposure to 200 ppb sulphur dioxide ( SO2 ) and 200 μg/m3 and 2000 μg/m3 aerosols of ammonium bisulphate ( AB ) and sulphuric acid ( SA ) ( MMD 0.3 μm ) . Methods : Exposures were placebo controlled , for one hour at rest , double blind in r and om order . ΔFEV1 was the primary outcome ; secondary outcomes included symptoms , ventilation , exhaled nitric oxide ( NO ) concentrations , and nasal lavage fluid ascorbic ( AA ) and uric acid ( UA ) concentrations . Results : There were no significant changes in spirometry or symptoms with any exposure in either group . SO2 exposure was associated with an increased respiratory rate relative to air exposure in the asthmatic group ( SO2 : 958.9 breaths/hour ; air : 906.8 breaths/hour ) but the mean volume breathed did not differ significantly ( SO2 : 318.8 litres ; air : 311.4 litres ) . AB exposures were associated with a significant rise in [ NO ] in the asthmatic ( + 1.51 ppb , and + 1.39 ppb ) , but not in the normal group . Mean pre- and post-exposure [ AA ] tended to be higher in the normal than in the asthmatic group . Within each group , [ AA ] did not change significantly with any exposure . Post-exposure [ UA ] were greater than pre-exposure concentrations for all exposures , significantly so in the normal group for all exposures except SO2 . There were no significant differences in the mean change in [ UA ] for any exposure relative to air . Conclusions : The pollutant exposure concentrations employed in this study were generally much greater than ambient . It is unlikely that short lived exposures at lower concentrations would show significant effects , but effects of longer term lower concentration exposures can not be ruled out Background : R and omised data in men show a small but significant reduction in the risk of adult-onset asthma among those given aspirin . The results from an observational study in women suggest that frequent use of aspirin decreases the risk of adult-onset asthma , but r and omised data in women are lacking . A study was undertaken to test the effect of 100 mg aspirin or placebo on alternate days on the risk of adult-onset asthma in the Women ’s Health Study . Methods : A r and omised , double-blind , placebo-controlled clinical trial of aspirin and vitamin E was performed in apparently healthy women with no indication or contraindication to aspirin therapy and no history of asthma at study entry . Female health professionals self-reported an asthma diagnosis on yearly question naires . Results : Among 37 270 women with no reported history of asthma prior to r and omisation and during 10 years of follow-up , there were 872 new cases diagnosed with asthma in the aspirin group and 963 in the placebo group ( hazard ratio 0.90 ; 95 % CI 0.82 to 0.99 ; p = 0.027 ) . This apparent 10 % lower relative risk of incident adult-onset asthma among those assigned to aspirin was significantly modified by body mass index , with no effect in women with a body mass index of ⩾30 kg/m2 . The effect  of aspirin on adult-onset asthma was not significantly modified by age , smoking status , exercise levels , postmenopausal hormone use or r and omised vitamin E assignment . Conclusions : In this large r and omised clinical trial of apparently healthy adult women , administration of 100 mg aspirin on alternate days reduced the relative risk of a newly reported diagnosis of asthma . Trial registration number : This pilot study aims to provide effect size confidence intervals , clinical trial and intervention feasibility data , and procedural material s for a full-scale r and omized controlled trial that will determine the efficacy of Dietary Approaches to Stop Hypertension ( DASH ) as adjunct therapy to st and ard care for adults with uncontrolled asthma . The DASH diet encompasses foods ( e.g. , fresh fruit , vegetables , and nuts ) and antioxidant nutrients ( e.g. , vitamins A , C , E , and zinc ) with potential benefits for persons with asthma , but it is unknown whether the whole diet is beneficial . Participants ( n = 90 ) will be r and omized to receive usual care alone or combined with a DASH intervention  consisting of 8 group and 3 individual sessions during the first 3 months , followed by at least monthly phone consultations for another 3 months . Follow-up assessment s will occur at 3 and 6 months . The primary outcome measure is the 7-item Juniper Asthma Control Question naire , a vali date d composite measure of daytime and nocturnal symptoms , activity limitations , rescue medication use , and percentage predicted forced expiratory volume in 1 second . We will explore changes in inflammatory markers important to asthma pathophysiology ( e.g. , fractional exhaled nitric oxide ) and their potential to mediate the intervention effect on disease control . We will also conduct pre-specified subgroup analyses by genotype ( e.g. , polymorphisms on the glutathione S transferase gene ) and phenotype ( e.g. , atopy , obesity ) . By evaluating a dietary pattern approach to improving asthma control , this study could advance the evidence base for refining clinical guidelines and public health recommendations regarding the role of dietary modifications in asthma management OBJECTIVE To determine if vitamin C ( ascorbic acid ) has a protective effect on the hyperreactive airways of patients with exercise-induced asthma ( EIA ) . DESIGN All the patients underwent pulmonary function tests at rest , before and 1 hour after receiving 2 g of oral ascorbic acid . They were then r and omly assigned in a double-blind manner to receive 2 g of ascorbic acid or a placebo 1 hour before a 7-minute exercise session on a treadmill . Pulmonary function tests  were performed after an 8-minute rest . This procedure was repeated 1 week later , with each patient receiving the alternative medication . SETTING A university hospital . PARTICIPANTS Twenty patients with asthma ( 13 males and 7 females ) , with ages ranging from 7 to 28 years ( mean , 13.8 years ) . All patients who had a decline of at least 15 % in their forced expiratory volume in 1 second after a st and ard exercise test on a motorized treadmill received a diagnosis of EIA . MAIN- OUTCOME MEASURES : All patients were advised to stop using their regular asthma medication or bronchodilator 12 hours before the test . Pulmonary function tests were performed in the same ambient conditions on all patients . RESULTS All patients received a diagnosis of EIA . Ascorbic acid administration did not change the results of pulmonary functions at rest after 1 hour . In 9 patients , a protective effect on exercise-induced hyperreactive airways was documented . Four of 5 patients who received ascorbic acid and documented a protective effect on EIA continued to receive ascorbic acid , 0.5 g/d , for 2 more weeks with the same protective effect . CONCLUSIONS The efficacy of vitamin C in preventing EIA can not be predicted . However , vitamin C may have a protective effect on airway hyperreactivity in some patients with EIA Exhaled carbon monoxide ( eCO ) is a potential non-invasive marker of airway inflammation . We have investigated the cross-sectional and longitudinal relationship between eCO and lung function and bronchial reactivity in 69 adults with atopic asthma , in the course of participation in a 6-week r and omised placebo-controlled trial of vitamin E supplementation .  At baseline , there was no cross-sectional association between absolute eCO levels and either forced expiratory volume ( FEV(1 ) ) , forced vital capacity ( FVC ) or bronchial reactivity . However , in the longitudinal analysis within the placebo group , a rise in mean eCO was significantly associated with improvement in bronchial reactivity ( change in eCO ( parts per million ) per natural log unit change in bronchial hyperreactivity 0.498 , 95 % confidence interval 0.071 to 0.924 , P=0.024 ) . These findings suggest that , contrary to previous data , there is no cross-sectional relationship between eCO and lung function or bronchial reactivity , but that there may be a longitudinal trend with bronchial reactivity that is worth further investigation OVER THE PAST THREE DECADES , many studies have been published of the associations between a variety of different measures of antioxidants and both  asthma and lung function .  While there is always a risk of publication bias , the general trend of these studies has been to suggest an association between higher dietary antioxidant intake with less asthma and better lung function . The study by Yoon et al. in this issue of the Journal adds to this body of literature by identifying 100 patients with relatively stable asthma , and demonstrating that those with a serum total antioxidant capacity ( TAC ) over the mean value have a higher baseline lung function than those with a serum TAC less than the mean value , although there was no signifi ca nt difference in bronchial reactivity.1 However , TAC levels were not signifi cantly correlated with longitudinal changes in pulmonary function , although the higher baseline lung function result ed in greater forced expiratory volume both one and two years after enrolment — as would probably be expected . As serum TAC refl ects a composite of endogenous and exogenous factors , only the latter category can be considered amenable to intervention . These include environmental tobacco exposure ( which was not adjusted for in the article by Yoon et al. ) , ambient pollution and dietary antioxidants.2 Recognition is growing of the importance of societal level interventions to reduce tobacco consumption and hence exposure to this and other forms of ambient pollution . The challenge for epidemiological research ers is to distinguish causality from association ; this is particularly true for nutritional research , where the problems of confounding by lifestyle , pre-natal exposures and possibly even pre-conception exposures ( via epigenetics ) are manifold . The only study design that can deliver these answers is the r and omised controlled trial , and these are better able to consider the secondary treatment of diseases such as asthma , rather than the primary prevention of asthma due to logistical considerations such as cost and recruitment . However , selection of the intervention is diffi cult , as relatively small studies ( compared to pharmaceutical studies ) of individual antioxidants have not been encouraging.3,4 One particular problem observed in these studies is that the individuals who volunteer to participate in these studies are often already eating a healthy diet , have an interest in healthy eating and hence may have little room for nutritional improvement . The most promising nutritional interventions in asthma have tended to involve combinations of antioxidants5 and , more recently , increased fruit and vegetable intake.6  The latter study suggested that those who received fi ve servings of vegetables and two servings of fruit daily were less than half as likely to have an exacerbation during the following 14 weeks . Further r and omised controlled studies of this nature are required to permit an enhanced underst and ing of the role of oxidation with regard to asthma aetiology and severity , and hopefully to permit translation of epidemiological observations into tangible effects from which the individual patient can benefi In this study , the perceptions of asthmatics to change in their disease was associated with observed changes in clinical asthma measures , in order to identify the threshold where changes in clinical asthma measures are perceivable by patients . The study included 281 asthmatic patients , aged 18 - 63 yrs , in a r and omized , placebo-controlled clinical trial of a leukotriene antagonist .  Changes were related in : 1 ) asthma symptom scores ; 2 ) inhaled beta-agonist use ; 3 ) forced expiratory volume in one second ( FEV1 ) ; and 4 ) peak expiratory flow ( PEF ) to a global question that queried overall change in asthma since starting the study drug . Additional analyses examined differences in the group reporting minimal improvement by treatment ( active treatment versus placebo ) , sex and age groups . The average minimal patient perceivable improvement for each measure was : 1 ) -0.31 points for the symptom score on a scale of 0 - 6 ; 2 ) -0.81 puffs x day(-1 ) for inhaled beta-agonist use ; 3 ) 0.23 L for FEV1 ; and 4 ) 18.79 L x min(-1 ) for PEF . In general placebo-treated patients and older patients , who reported minimal improvement , experienced less mean improvement from baseline than active-treated patients and younger patients , who reported minimal improvement . Determining the minimal patient perceivable improvement value for a measure may be helpful to interpret changes . However , interpretation should be carried out cautiously when reporting a single value as a clinical ly important change This present trial investigated the efficacy of supplementation with Chlorella vulgaris , a bioactive microalga rich in macro- and micronutrients , in the improvement of biochemical and clinical symptoms in patients with obstructive pulmonary disorders . Ninety-seven patients with chronic obstructive pulmonary disease ( COPD ) or asthma who were under conventional treatment regimens were r and omly assigned to C. vulgaris extract ( CVE ) ( n=48 ; 2700 mg/day ) or no adjunctive therapy ( n=49 ) for eight weeks . Serum levels of antioxidants along with spirometric parameters and clinical symptoms were evaluated pre- and post-trial . The magnitude of increases in the concentrations of glutathione , vitamin E , and vitamin C , and activities of glutathione peroxidase , catalase , and superoxide dismutase enzymes were all significantly greater in the CVE vs. control group ( p<0.05 ) . In spite of increases , none of the assessed spirometric parameters ( FVC , FEV1 , FEV1/FVC , and FEF25–75 % ) did significantly differ by the end of the trial in the study groups , apart from a significant elevation of FEV1 in the control group ( p=0.03 ) . The frequency of coughing , shortness of breath , wheezing , and sputum brought up were all significantly reduced in both CVE and control groups ( p<0.05 ) . The rate of improvement for sputum brought up and wheezing were significantly greater in the CVE group compared to the control group ( p<0.05 ) . Although CVE was found to ameliorate serum antioxidant status , its supplementation was not associated with any bronchodilatory activity . The results of the present trial do not support any clinical efficacy for CVE in patients with obstructive pulmonary disorders PURPOSE The purpose of this study was to test the effectiveness of an integrative medicine approach to the management of asthma compared to st and ard clinical care on quality of life ( QOL ) and clinical outcomes . METHODS This was a prospect i ve parallel group repeated measurement r and omized design . Participants were adults aged 18 to 80 years with asthma . The intervention consisted of six group sessions on the use of nutritional manipulation , yoga techniques , and journaling . Participants also received nutritional supplements : fish oil , vitamin C , and a st and ardized hops extract . The control group received usual care . Primary outcome measures were the Asthma Quality of Life Question naire ( AQLQ ) , The Medical Outcomes Study Short Form-12 ( SF-12 ) , and st and ard pulmonary function tests ( PFTs ) . RESULTS In total , 154 patients were r and omized and included in the intention-to-treat analysis ( 77 control , 77 treatment ) . Treatment participants showed greater improvement than controls at 6 months for the AQLQ total score ( P<.001 ) and for three subscales , Activity ( P < 0.001 ) , Symptoms ( P= .02 ) , and Emotion ( P<.001 ) . Treatment participants also showed greater improvement than controls on three of the SF-12 subscales , Physical functioning ( P=.003 ) ; Role limitations , Physical ( P < .001 ) ; and Social functioning ( P= 0.03 ) , as well as in the aggregate scores for Physical and Mental health ( P= .003 and .02 , respectively ) . There was no change in PFTs in either group . CONCLUSION A low-cost group-oriented integrative medicine intervention can lead to significant improvement in QOL in adults with asthma Introduction Our study was undertaken to determine the association between use of a health plan-sponsored health club benefit by older adults and total health care costs over 2 years . Methods This retrospective cohort study used administrative and cl aims data from a Medicare Advantage plan . Participants ( n = 4766 ) were enrolled in the plan for at least 1 year before participating in the plan-sponsored health club benefit ( Silver Sneakers ) . Controls ( n = 9035 ) were matched to participants by age and sex according to the index date of Silver Sneakers enrollment .  Multivariate regression models were used to estimate health care use and costs and to make subgroup comparisons according to frequency of health club visits . Results Compared with controls , Silver Sneakers participants were older and more likely to be male , used more preventive services , and had higher total health care costs at baseline . Adjusted total health care costs for Silver Sneakers participants and controls did not differ significantly in year 1 . By year 2 , compared with controls , Silver Sneakers participants had significantly fewer inpatient admissions ( −2.3 % , 95 % confidence interval , −3.3 % to −1.2 % ; P < .001 ) and lower total health care costs ( −$500 ; 95 % confidence interval , −$892 to −$106 ; P = .01 ] . Silver Sneakers participants who averaged at least two health club visits per week over 2 years incurred at least $ 1252 ( 95 % confidence interval , −$1937 to −$567 ; P < .001 ) less in health care costs in year 2 than did those who visited on average less than once per week . Conclusion Regular use of a health club benefit was associated with slower growth in total health care costs in the long term but not in the short term . These findings warrant additional prospect i ve investigations to determine whether policies to offer health club benefits and promote physical activity among older adults can reduce increases in health care costs Airway mucus hypersecretion and increased oxidative stress are clinical and pathophysiological features of asthma exacerbation . We studied effects of N-acetylcysteine ( NAC ) as a mucolytic and antioxidant agent in asthma exacerbation . In this r and omized , single-blinded , placebo-controlled study 50 patients ( 17 male , 33 female , mean age 48.94+/-13.68 ) with asthma exacerbation were r and omized to receive either oral 600 mg b.d . N-acetylcysteine or placebo in addition to st and ard treatment during 5 days hospitalization . Daily measurements of wheezing , dyspnea , cough , sputum , expectoration , night sleep scores and morning PEFR were performed . There was no significant difference in wheezing score between patients assigned NAC and those assigned placebo in day 5(0.84[SD 0.94 ] VS 0.87[SD 0.79 ] ) and also in cough score ( 0.72[SD 0.84 ] VS 0.79[SD 0.97 ] ) , dyspnea score ( 0.84[SD 1.06 ] VS 0.91[SD 1.01 ] ) , sputum score(0.79[SD 0.83 ] VS 0.62[SD 0.71 ] ) , expectoration score(0.79[SD 0.97 ] VS 0.83[SD 1.09 ] ) , night sleep score(1[SD 1.17 ] VS 0.67[SD 0.98 ] and morning PEFR ( 256[SD 96.36 ] VS 282[SD 98.86 ] ) . We concluded that addition of N-acetylcysteine to usual asthma medication has no significant effect in treatment of asthma exacerbation BACKGROUND Previous research has shown that diet can modify the bronchoconstrictor response to exercise in asthmatic subjects . OBJECTIVE Determine the effect of ascorbic acid supplementation on pulmonary function and several urinary markers of airway inflammation in asthmatic subjects with exercise-induced bronchoconstriction ( EIB ) . METHODS Eight asthmatic subjects with documented EIB participated in a r and omized , 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 ( 1500 mg/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 9alpha , 11beta-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 9alpha , 11beta-PGF2 concentration was significantly lower ( p<0.05 ) on the ascorbic acid diet compared to the placebo and usual diet . CONCLUSION Ascorbic acid supplementation provides a protective effect against exercise-induced airway narrowing in asthmatic subjects Antioxidant-rich diets are associated with reduced asthma prevalence . However , direct evidence that altering intake of antioxidant-rich foods affects asthma is lacking . The objective was to investigate changes in asthma and airway inflammation result ing from a low antioxidant diet and subsequent use of lycopene-rich treatments .  Asthmatic adults ( n=32 ) consumed a low antioxidant diet for 10 days , then commenced a r and omized , cross-over trial involving 3 × 7 day treatment arms ( placebo , tomato extract ( 45 mg lycopene/day ) and tomato juice ( 45 mg lycopene/day ) ) . With consumption of a low antioxidant diet , plasma carotenoid concentrations decreased , Asthma Control Score worsened , % FEV1 and % FVC decreased and % sputum neutrophils increased . Treatment with both tomato juice and extract reduced airway neutrophil influx . Treatment with tomato extract also reduced sputum neutrophil elastase activity . In conclusion , dietary antioxidant consumption modifies clinical asthma outcomes . Changing dietary antioxidant intake may be contributing to rising asthma prevalence . Lycopene-rich supplements should be further investigated as a therapeutic intervention BACKGROUND We recently reported that antioxidant supplementation with vitamins C and E mitigated ozone related decline in forced expiratory flow ( FEF(25 - 75 ) ) in 158 asthmatic children in an area with high ozone exposure in Mexico City . METHODS A study was undertaken to determine whether deletion of glutathione S-transferase M1 ( GSTM1 null genotype ) , a gene involved in response to oxidative stress , influences ozone related decline in FEF(25 - 75 ) and the benefit of antioxidant supplementation . RESULTS GSTM1 null children receiving placebo had significant ozone related decrements in FEF(25 - 75 ) ( percentage change per 50 ppb of ozone 2.9 ( 95 % CI -5.2 to -0.6 ) , p=0.01 ) ; GSTM1 positive children did not . Conversely , the effect of antioxidants  was stronger in children with the GSTM1 null genotype . CONCLUSIONS Asthmatic children with a genetic deficiency of GSTM1 may be more susceptible to the deleterious effects of ozone on the small airways and might derive greater benefit from antioxidant supplementation Associations have been reported between suboptimal maternal vitamin E intake during pregnancy and childhood asthma . This pilot study conducted in 2008/2009 investigated the feasibility and acceptability of a food-based r and omized controlled trial in pregnant women to optimize dietary vitamin E intake to 15 mg/day . A food-based intervention using " food exchanges " to individually optimize dietary vitamin E intake to 15 mg/day was developed and included in an advice booklet . Forty-three pregnant women with a personal/partner history of asthma were recruited at 12 weeks gestation and r and omized to food-based intervention or a control group until 20 weeks gestation . A registered dietitian assessed the  vitamin E intake of 22 women and provided tailored advice on food-based exchanges to optimize their intake to 15 mg/day . The 21 control women were not given dietary advice . The food-based intervention was completed by 19 women and increased mean vitamin E intake : food diary data , 7.13 mg/day ( 95 % confidence interval : 5.63 to 18.6 ) to 17.4 mg/day ( 95 % confidence interval : 14.4 to 20.5 ) ( P<0.001 ) . This pilot study demonstrates the feasibility and acceptability of a food-exchange-based intervention to  optimize dietary vitamin E intake during pregnancy . Additional work is required to determine whether this intervention , if sustained for the rest of pregnancy , reduces the likelihood of childhood asthma . The methodology used in the design of this novel food-based intervention could be transferred to other nutrients To further establish the role of oxidative stress in the pathogenesis of acute bronchial asthma , we investigated the effects of platelet-activating factor ( PAF ) challenge on systemic oxidant-antioxidant balance in 12 asthmatic patients ( age , 25+/-3[SEM ] yr ; FEV1 , 95+/-10 % predicted ) , using a double blinded , controlled with Lyso-PAF ( L-PAF ) , cross-over design . Respiratory system resistance ( Rrs ) , arterial blood gases , peripheral blood neutrophils and oxidant-antioxidant balance , including thiobarbituric acid (TBA)-malondialdehyde ( MDA ) adducts , protein sulphydryls and Trolox equivalent antioxidant capacity ( TEAC ) , were assessed at baseline and 5 , 15 and 45 min after PAF and L-PAF ( 18 microg each ) bronchoprovocation . Urinary leukotriene E4 ( uLTE4 ) elimination was measured 120 min after challenge . Compared with baseline , as expected , PAF increased significantly Rrs and AaPO2 and decreased PaO2 and peripheral blood neutrophils along with a rebound neutrophilia and increased uLTE4 . By contrast , markers of systemic oxidative stress remained unaltered throughout the study . Unlike PAF , L-PAF-induced changes were negligible . We conclude that there is no systemic oxidant-antioxidant imbalance during acute bronchoconstriction induced by PAF in these patients with mild asthma BACKGROUND Chronic airway inflammation in asthma or chronic obstructive pulmonary disease ( COPD ) may be involved in the pathogenesis of type 2 diabetes ; however , prospect i ve data have been limited . METHODS A prospect i ve cohort of 38,570 women who were aged ≥ 45 years , free of cardiovascular disease and cancer at baseline , and free of diabetes at baseline and in the first 12 months were analyzed . We classified all women into three groups according to the presence and absence of self-reported asthma or COPD ( including emphysema , chronic bronchitis , and bronchiectasis ) . RESULTS During a median follow-up of 12.2 years , 2472 incident type 2 diabetes  events were documented . Women who had ever reported asthma or COPD were associated with an increased diabetes risk ; the multivariate RRs were 1.37 ( 95 % CI , 1.20 - 1.57 ) for women who had asthma alone and 1.38 ( 95 % CI , 1.14 - 1.67 ) for COPD without asthmatic symptoms . Furthermore , these associations were not significantly modified by age , smoking status , physical activity , BMI , alcohol intake , hormone replacement therapy , menopausal status or r and omized treatment . CONCLUSIONS Asthma and COPD were individually and independently associated with an increased risk of type 2 diabetes in women , indicating that chronic airway inflammation may contribute to diabetes pathogenesis Background Epidemiological studies suggest that higher intakes of dietary vitamin C and magnesium may be associated with a reduced risk of asthma To evaluate whether acute effects of ozone , nitrogen dioxide , and particulates with mass median diameter less than 10 micro m could be attenuated by antioxidant vitamin supplementation , we conducted a r and omized trial using a double-blinded design . Children with asthma ( n = 158 ) who were residents of Mexico City were r and omly given a daily supplement of vitamins ( 50 mg/day of vitamin E and 250 mg/day of vitamin C ) or a placebo and were followed from October 1998 to April 2000 . Pulmonary function tests were carried out twice a week in the morning . During the follow-up observation period , the mean 1-hour maximum ozone level was 102 ppb ( SD = 47 ) , and the mean 24-hour average PM(10 ) level was 56.7 micro g/m(3 ) ( SD = 27.4 ) . In children with moderate and severe asthma , ozone levels 1 day before spirometry were inversely associated significantly with forced expiratory flow ( FEF(25 - 75 ) ) ( -13.32 ml/second/10 ppb ; p = 0.000 ) , FEV(1 ) ( -4.59 ml/10 ppb ; p = 0.036 ) , and peak expiratory flow ( PEF ) ( -15.01 ml/second/10 ppb ; p = 0.04 ) in the placebo group after adjusting for potential confounding factors . No association between ozone and lung functions was observed in the supplement group . We observed significant differences in lung function decrements between groups for FEF(25 - 75 ) and PEF . Our results suggest that supplementation with antioxidants might modulate the impact of ozone exposure on the small airways of children with moderate to severe asthma To determine if micronutrient intake is associated with asthma severity , we administered the Block food frequency question naire to participants in a r and omized clinical trial of the safety of influenza vaccine for asthmatics . The nutrition sub study included 1033 participants , aged 12–75 . Intake of antioxidant vitamins , soy isoflavones , total fruits and vegetables , fats , and fiber was compared with asthma severity at baseline [ forced expiratory volume in 1 second ( FEV1 ) , peak expiratory flow rate ( PEF ) , asthma symptoms ] and the rate of asthma exacerbations during the 2 weeks following influenza vaccination . The only nutrient that had a consistent association with asthma severity was genistein , a soy isoflavone . None of the nutrients evaluated were related to asthma exacerbation rate when adjusted for known confounders . The FEV1 in genistein consumers of at least 250 µg/1000 Kcal/day was 82.1 % predicted , 79.9 % predicted for those who consumed between 1 and 249 µg/1000 kcal , and 76.2 % predicted in genistein nonconsumers ( p = 0.006 ) ; the PEF was 82.7 % predicted , 80.8 % predicted , and 78.3 % predicted , respectively ( p = 0.009 ) . There were no differences in the Asthma Symptom Utility Index ( ASUI ) . We could not account for these results based on differences in demographics , body mass index , or consumption of other nutrients . Thus , increasing consumption of genistein is associated with better lung function in patients with asthma . Further studies are needed to determine whether dietary supplementation with genistein can reduce asthma severity The human lung , due to the oxidative and ozone stress to which it is exposed , is particularly vulnerable to oxidative damage . Concentrations of dietary antioxidants in the lung epithelial lining and lining fluids may provide protection against oxidative damage . A r and omized clinical trial was conducted to study the effects of supplemental , carotenoid-rich vegetable Juice ( V-8 ) on lung function macrophage levels of carotenoids and in moderating ozone-induced lung damage . Healthy young adults ( n = 23 ) were exposed to 0.4 ppm ozone in a chamber for 2 hr after either 2 weeks of antioxidant supplementation ( including one can of V-8 juice daily ) or placebo .  Mean lung concentrations of lycopene increased by 12 % , and lung epithelial cell DNA damage as measured by the Comet Assay decreased 20 % In supplemented subjects . No change in peripheral blood lymphocyte DNA damage was observed as evidence d by no change in mean comet area or length in supplemented or placebo subjects . We were not able to separate the effects of lycopene from other carotenoids or antioxidants administered in this study ; however , lycopene is the predominant carotenold in V-8 ( it represents 88 % of total carotenoids ) . A review of the epidemiologic literature providing evidence for the effect of lycopene ( diet or serum ) or tomatoes on the risk of lung cancer reveals 27 observational epidemiologic studies ( 18 case-control and nine cohort studies ) reporting relative risk ( RR ) estimates . RR estimates for cohort studies ranged from 0.63 to 1.24 ( mean RR = 0.93 , SD = 0.16 ) . Odds ratios ( OR ) for case-control studies ranged from 0.27 to 0.93 ( mean OR = 0.61 , SD = 0.16 ) . Both plasma levels ( RR = 1.01 , OR = 0.37 ) and estimated intakes of lycopene from dietary sources ( mean RR = 0.93 , RR range = 0.80–1.05 ; mean OR = 0.67 , OR range = 0.27–0.93 ) were examined . Seventeen studies , three of which were cohorts , reported their results at the level of tomato consumption rather than , or in addition to , lycopene consumption ( mean RR = 0.89 , RR range = 0.63–1.24 ; mean OR = 0.61 , OR range = 0.37–0.80 ) . The published epidemiologic literature shows an Interaction between study design and the relationship between lycopene and /or tomatoes and risk of lung cancer . Overall , cohort studies did not show an association , whereas case-control studies showed a decreased risk with greater consumption of lycopene and tomatoes . Altough lycopene can be found in the human lung , and there is evidence , albeit weak , for a protective association with lung cancer , its biologic role remains to be eluci date The effect of vitamin C pretreatment in preventing ragweed-induced bronchospasm was evaluated in 6 ragweed-sensitive asthmatics studied in a double-blind r and omized fashion . The patients received either lactose capsules or 500 mg of ascorbic acid and were studied out of season . Antigen dose-response curves were determined prior to the administration of lactose or ascorbic acid in each individual subject and subsequently after administration of ascorbic acid or lactose . Bothe PD20FEV1 ( provocation dose necessary for a 20 % reduction in forced expiratory volume in 1 second ) and PD35SGaw ( provocation dose necessary for a 35 % reduction in specific airways conductance ) were determined . In none of the six patients was there a change in baseline FEV 1 ( p greater than 0.70 ) nor the overall average baseline specific airways conductance ( rho greater than 0.90 ) . Additionally , no statistically significant difference ( p greater than 0.60 ) was noted between log PD35SGaw vitamin C day and lactose day . Likewise , no statistically significant difference ( p greater than 0.60 ) was evident when comparing log PD20FEV1 lactose and ascorbic acid days . Vitamin C ( 500 MG ) HAS NO PROTECTIVE EFFECT AGAINST RAGWEED ANTIGEN-INDUCED BRONCHOSPASM Selenium ( Se ) deficiency attenuates the host immune response , thereby increasing the risk of bacterial and viral infections . We have examined the effects of selenium supplementation ( SeS ) in corticoid-dependent asthmatics ( CDAs ) with lowered circulatory Se status . Twenty CDAs ( 10 males and 10 females , average age 54.5 yrs ) were enrolled into the study . The average duration of the disease was 10 yrs . The asthmatics were receiving 200 micrograms of Se per day for a period of 6 months , in addition to regular treatment with inhaled corticosteroids and beta-agonists . The expression of adhesion molecules ( CD11a , CD11b , CD18 , CD49d , CD54 , CD62L ) on peripheral blood mononuclear cells ( P BMC s ) of asthmatics and the expression of E- and P-selectins , ICAM-1 , VCAM-1 on cultured human umbilical vein endothelial cells ( HUVEC ) after stimulation with P BMC s from CDAs before and after 3 and 6 months of SeS were assessed by st and ard monoclonal antibodies and analyzed by flow cytometry . The concentrations of soluble adhesion molecules P-selectin , E-selectin , ICAM-1 and VCAM-1 were determined by ELISA method . The expression of adhesion molecules on P BMC s : After 3- and 6-months of SeS , a decreased expression of molecules CD11a , CD11b and CD62L was observed ( p < 0.02 , p < 0.005 , p < 0.003 ) . No changes were seen in the expression of CD18 , CD49d except for the increased expression of CD54 ( p < 0.005 ) . Modulation of adhesion molecules expression on HUVEC : We observed a significant increase in VCAM-1 , P- and E-selectins expressions in the group of asthmatics without SeS in comparison with the control group ( p < 0.05 , p < 0.01 , p < 0.05 ) . During SeS a significant decrease in molecules VCAM-1 , E-selectin ( after 3 months ) ( p < 0.05 , p < 0.05 ) and P-selectins and ICAM-1 ( after 6 months ) ( p < 0.05 , p < 0.01 ) were observed . Soluble adhesion molecules : After 3 months of SeS we noticed a significant decrease in VCAM-1 and P-selectin expressions ( p < 0.05 , p < 0.05 ) and after 6 months the level of VCAM-1 decreased ( p < 0.01 ) . The effect of Se on the adhesion molecules expression in endothelial cells in vitro experiments : Se blocks the expression of adhesion molecules stimulated by IFN-gamma in a dose-dependent way after addition of Se into a culture of endothelial cells . Concentration of 10 micrograms/ml inhibits the increase in expression of ICAM-1 ( p < 0.05 ) but not that of VCAM-1 , E- or P-selectins . The inhibition of expression in Se concentration of 10 micrograms/ml is over 80 % ( p < 0.01 ) . Our data demonstrate that Se is able to affect the adhesion molecules expressions that are crucial in the inflammatory process . ( Fig. 5 , Ref . 22 . STUDY OBJECTIVES To characterize asthma symptoms and pulmonary function throughout two menstrual cycles , with and without exogenous estradiol administration , in women with premenstrual asthma , and to determine the effect of estradiol administration on asthma symptoms , pulmonary function , quality of life , and biomarkers of airway inflammation . DESIGN Double-blind , r and omized , placebo-controlled , crossover study . SETTING Respiratory clinic and clinical research center . SUBJECTS Twelve women with documented premenstrual asthma ( > or = 20 % premenstrual worsening of asthma symptoms and /or of peak expiratory flow [ PEF ] during a 1-month screening phase ) . INTERVENTION Each woman received either estradiol 2 mg or placebo orally between cycle days 23 and 28 ( i.e. , premenstrually , or before the onset of menses ) in the first cycle and then crossed over to the other arm in the second cycle . Throughout both cycles , the women recorded daily morning and evening PEF readings and asthma symptoms . MEASUREMENTS AND MAIN RESULTS Spirometry testing and measurement of serum estradiol and biomarkers of airway inflammation were performed on days 8 ( follicular phase ) , 22 ( luteal phase ) , and 28 ( premenstrually ) of both the estradiol and placebo cycles . During the two premenstrual visits , the Asthma Quality of Life Question naire was administered . No notable differences were observed between the estradiol and placebo cycles in daily PEF recordings or composite asthma symptoms scores . The area under the curve ( AUC ) for the composite asthma symptoms versus time profile was numerically , but not statistically , lower ( denoting less severe symptoms ) during the estradiol cycle than during the placebo cycle . Likewise , no significant difference in AUC values for morning PEF or evening PEF was found between the estradiol cycle and the placebo cycle . Despite differences ( p<0.05 ) in day-28 estradiol concentrations for estradiol and placebo cycles , no significant differences were found in forced expiratory volume in 1 second , serum endothelin-1 , serum and urine eosinophil protein X , urine leukotriene E4 , or quality -of-life scores . CONCLUSION Exogenously administered estradiol did not have a significant effect in women with premenstrual asthma whose asthma was classified predominantly as mild and under excellent control . As in the case of premenstrual syndrome , the placebo effect may be prominent in premenstrual asthma . Further trials , involving women with more severe asthma under poorer control , are warranted to discern underlying mechanisms for the worsening of asthma in relation to menstruation A r and omized , placebo‐controlled , double‐blind study involving 60 subjects , aged 6–18 years old , was conducted over a period of 3 months to determine the effect of Pycnogenol ® ( a proprietary mixture of water‐soluble bioflavonoids extracted from French maritime pine ) on mild‐to‐moderate asthma . After baseline evaluation , subjects were r and omized into two groups to receive either Pycnogenol ® or placebo . Subjects were instructed to record their peak expiratory flow with an Assess ® Peak Flow Meter each evening . At the same time , symptoms , daily use of rescue inhalers ( albuterol ) , and any changes in oral medications were also recorded . Urine sample s were obtained from the subjects at the end of the run‐in period , and at 1‐ , 2‐ , and 3‐month visits . Urinary leukotriene C4/D4/E4 was measured by an enzyme immunoassay . Compared with subjects taking placebo , the group who took Pycnogenol ® had significantly more improvement in pulmonary functions and asthma symptoms .  The Pycnogenol ® group was able to reduce or discontinue their use of rescue inhalers more often than the placebo group . There was also a significant reduction of urinary leukotrienes in the Pycnogenol ® group . The results of this study demonstrate the efficacy of Pycnogenol ® as an adjunct in the management of mild‐to‐moderate childhood asthma Abstract Ozone exposure aggravates  asthma  , as has been demonstrated in both controlled exposures and epidemiologic studies . In the current double-blind crossover study , the authors evaluated the effects of dietary antioxidants ( i.e. , 400 IU vitamin E/500 mg vitamin C ) on ozone-induced bronchial hyperresponsiveness in adult subjects with asthma . Seventeen subjects were exposed to 0.12 ppm of ozone or to air for 45 min during intermittent moderate exercise .  Bronchial hyperresponsiveness was assessed with 10-min sulfur dioxide ( i.e. , 0.10 ppm and 0.25 ppm ) inhalation challenges . Subjects who were given dietary antioxidants  responded less severely to sulfur dioxide challenge than subjects given a placebo ( i.e. , forced expiratory volume in the 1st sec : -1.2 % vs. 4.4 % , respectively ; peak flow : + 2.2 % vs. -3.0 % , respectively ; and mid-forced expiratory flow : + 2.0 % vs. -4.3 % , respectively ) . Effects were more pronounced when subjects were grouped by response to sulfur dioxide at the screening visit . The results suggest that dietary supplementation with vitamins E and C benefits asthmatic adults who are exposed to air pollutants To eluci date the effect of antioxidants aevit and glutaminic acid on the course of bronchial asthma ( BA ) and free radical processes in this disease , 54 BA patients were divided into 2 groups : glucocorticoid-untreated and glucocorticoid-treated . Each of two subgroups made of these groups either received antioxidants ( AO ) or not . The response was assessed by clinical BA symptoms and free radical processes reflecting production of active oxygen forms by leukocytes ( PAOFL ) and free radical peroxidation ( FRPO ) . PAOFL was studied using luminol-dependent chemiluminescence ( CL ) . CL basal and stimulated values were calculated . FRPO was measured by plasma levels of malonic dialdehyde .  Aevit and glutaminic acid treated BA patients improved clinical ly and exhibited reduced CL of PAOFL and malonic dialdehyde in plasma compared to BA patients on conventional therapy or conventional therapy plus glucocorticoids . Aevit and glutaminic acid are recommended for BA patients Methods Mild asthmatics and normal controls were recruited as study subjects . This crossover study was double-blinded , r and omized and counter-balanced to the order of three conditions : diesel exhaust with anti-oxidant , diesel exhaust with placebo , or filtered air with placebo . The subjects were exposed to either filtered air or diesel exhaust ( 300 ug PM2.5/m ) in a state-of-the-art diesel exhaust exposure facility . An anti-oxidant , N-acetylcysteine ( 600 mg ) , or a placebo was taken orally for five days preceding , and on the day of the exposure . Each subject was exposed to each of the three conditions .  Peripheral blood sample s were taken pre-exposure , and also at 2 , 6 , and 30 hours after the beginning of exposure . Sputum induction was performed by inhalation of hypertonic saline according to ATS guidelines pre-exposure , and also at 6 , and 30 hours after the beginning of exposure . FACSCanto II ( BD Biosciences ) was used for flow cytometry . A 5-colour , 12-marker ( CD3/CD9/ CD14/CD16/CD19/CD20/CD45/CD56/CD83/CD206/ CD326/HLA-DR ) combination was used to identify dendritic cells , macrophages , monocytes , neutrophils , eosinophils , and bronchial epithelial cells . Direct immunolabelling was performed on whole peripheral blood . After incubation , red blood cells were lysed . Remaining cells were washed and resuspended in PBS with 0.5 % paraformaldehyde . Sputum plugs were homogenized with 0.1 % DTT , filtered , and then centrifuged to remove supernatant . Sputum cells were resuspended in PBS at 1 million per mL. Direct immunolabelling was performed . After incubation , cells were washed and resuspended in PBS with 0.5 % paraformaldehyde . Spectral compensation for flow cytometry was performed using an automatic calibration technique ( BD CompBeads ) . Cellular debris was eliminated on the SSC/FSC scattergram . A gating strategy was design ed to identify the leukocyte sub- population s and bronchial epithelial cells . Surface markers were chosen based on differential cell-specific expression according to existing literature Background : Increased dietary vitamin E intake is associated with a reduced incidence of asthma , and combinations of antioxidant supplements including vitamin E are effective in reducing ozone induced bronchoconstriction . A study was undertaken to investigate the effect of supplementation with vitamin E for 6 weeks on bronchial hyperresponsiveness in atopic adults with asthma . Methods : 72 participants from a clinical trial register of adults with asthma were r and omised to receive 500 mg natural vitamin E or matched placebo for 6 weeks in a placebo controlled , double blind parallel group clinical trial . Inclusion criteria included age 18–60 years , maintenance treatment of at least one dose of inhaled corticosteroid per day , a positive skin prick test to one of three common allergens , and bronchial hyperresponsiveness to methacholine ( defined as a dose provoking a 20 % fall in forced expiratory volume in 1 second ( FEV1 ) ( PD20 ) of 12.25 μmol ) . Secondary outcomes were FEV1 , forced vital capacity , mean morning and evening peak flow , symptom scores , bronchodilator use , and serum immunoglobulin E levels . Results : In the primary intention to treat analysis the change in PD20 was similar in the vitamin E and placebo groups with a mean difference of + 0.25 doubling doses of methacholine ( 95 % confidence interval −0.67 to + 1.16 greater with vitamin E ) . There was no effect of vitamin E supplementation on any other measure of asthma control , either in the intention to treat or per protocol analysis . There was also no effect of vitamin E supplementation on serum immunoglobulin levels . Conclusion : Dietary supplementation with vitamin E adds no benefit to current st and ard treatment in adults with mild to moderate asthma Forty-one asthmatic patients in remission were r and omly allocated to two treatment groups in a double-blind trial . One group took 1 g , of ascorbic acid as one effervescent tablet once daily and the second group took a matching placebo .  The asthmatics were selected from those attending the Asthma Clinic . One criterion for selection was the increase in exacerbation during the rainy season . These exacerbations were precipitated by respiratory infection . After 14 weeks , an assessment of the severity and rate of attacks showed that those on ascorbic acid suffered less severe and less frequent attacks of asthma during the study period . Plasma ascorbic acid astimations showed a significant rise in the level in those taking ascorbic acid over those on placebo . ( P < 0.01 ) . Cessation of ascorbic acid in the group taking it increased attack rates . It is concluded that high dose ascorbic acid is probably a good prophylaxis in some bronchial asthmatics Sixteen White children with bronchial asthma were divided into two groups ; one received st and ard anti-asthma chemoprophylaxis ( SAC ) and the other SAC supplemented with 1 g ascorbic acid ( Redoxon ) given as a single daily dose for a 6-month period . In 10 patients the effects of ascorbic acid on exercise-induced bronchoconstriction ( EIB ) were assessed by comparing the pre-ascorbic acid results with those obtained 2 1/2 hours after the intravenous injection of 1 g ascorbic acid . Immunological investigations performed on the two groups were assessment of polymorphonuclear leucocyte ( PMNL ) motility , phagocytosis and nitroblue tetrazolium reduction and measurement of secretory IgA , serum immunoglobulin and total haemolytic complement levels and levels of the components C3 and C4 , alpha 1-antitrypsin , antistreptolysin O ( ASO ) , C-reactive protein and antibodies to certain respiratory viruses . These investigations were performed before and 1 , 3 and 6 months after the commencement of therapy . Radio-allergosorbent testing for sensitivity to four common allergens was carried out at the outset and after 6 months of therapy . Injection of ascorbic acid had no detectable effects on the degree of EIB . Slight but not significant immunological changes were observed in the SAC group over the 6-month study period . However , in the SAC plus ascorbic acid group significantly improved PMNL motility and decreased ASO levels and reduced ( although not to a significant extent ) IgE levels and titres of antibodies to the respiratory viruses were observed PURPOSE Reactive oxygen/nitrogen species ( ROS/RNS ) in resident airway cells may be important in bronchoconstriction following exercise . Glutathione ( GSH ) is a major lung antioxidant and could influence pathological outcomes in individuals with exercise-induced bronchoconstriction ( EIB ) . This study examined the effects of supplementation with undenatured whey protein ( UWP ) in subjects exhibiting airway narrowing following eucapnic voluntary hyperventilation ( EVH ) , a surrogate challenge for diagnosis of EIB . UWP is a cysteine donor that augments GSH production . METHODS In a r and omized , double-blind , placebo-controlled study , 18 EIB-positive subjects ( age : 25.2 + /- 9.01 yr ; weight : 77.3 + /- 18.92 kg ; height : 1.7 + /- 0.09 m ) with post-EVH falls of > or = 10 % in FEV1 received 30 g UWP ( TX ) or casein placebo (PL)/d . Subjects performed 6-min EVH challenges before and after 4 and 8 wk of supplementation . Exhaled nitric oxide ( eNO ) was measured serially before spirometry and at 1-wk intervals . Spirometry was performed pre- and 5 , 10 , and 15 min postchallenge . RESULTS Subjects exhibited significant mean improvement in postchallenge falls in FEV(1 ) from 0 wk ( -22.6 + /- 12.22 % ) with TX at 4 ( -18.9 + /- 12.89 % , P < 0.05 ) and 8 wk ( -16.98 + /- 11.61 % , P < 0.05 ) and significant mean reduction in post-EVH peak falls in FEF(25 - 75 ) from 0 wk ( -40.6 + /- 15.28 % ) with TX at 4 ( -33.1 + /- 17.11 % , P < 0.01 ) and 8 ( -29.7 + /- 17.42 % , P < 0.05 ) wk . No changes in FEV(1 ) or FEF(25 - 75 ) were observed in the PL group at any time point . Mean eNO for PL and TX groups at 0 , 4 , and 8 wk ( 46.8 + /- 31.33 , 46.5 + /- 35.73 , 49.3 + /- 37.12 vs 35.2 + /- 26.87 , 29.1 + /- 17.26 , 34.7 + /- 21.11 ppb , respectively ) was not significantly different . CONCLUSIONS UWP may augment pulmonary antioxidant capacity and be therapeutically beneficial in individuals exhibiting EIB , as postchallenge pulmonary function improved with supplementation . The lack of significant change in eNO suggests that the pulmonary function improvements from UWP supplementation are independent of eNO Two groups of six asthmatic patients with biphasic bronchospastic response to inhaled Dermatophagoides pteronyssinus allergen extract were studied in a double-blind fashion . Early and late asthmatic reactions to allergen inhalation challenge were determined before and at the end of a 2-week treatment period with nimesulide ( 100 mg bid orally ) , a sulfonanilide with antioxidant properties , or placebo .  Bronchial responsiveness to methacholine was evaluated 24 hours before and after allergen inhalation challenges . The dose of allergen causing EAR ( 15 % decrease in FEV1 ) and the severity of LAR ( maximum FEV1 fall ) were similar before and at the end of the treatment period in both groups . In patients treated with nimesulide , bronchial responsiveness to methacholine was significantly increased after allergen inhalation challenge both before and at the end of the treatment period . These results do not support the hypothesis that the production of oxygen-free radicals plays a significant role in the development of bronchial hyperresponsiveness and late phase reaction to allergen in asthma PURPOSE To evaluate the association between active and passive smoking and  frequency of colds in women . METHODS Data on cigarette smoking and frequency and duration of colds were analyzed in the Women 's Health Study ( WHS ) , a r and omized , double-blind , placebo-controlled trial of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer among 39,876 female health professionals . RESULTS After adjustment for age , body-mass index , prevalence of asthma and chronic lung diseases , alcohol intake , physical activity , and multivitamin use , current heavy smokers had no appreciable increase in the frequency of colds ( relative risk ( RR ) for > or= 3 versus no colds in the past year , 1.05 ; 95 % confidence interval ( CI ) , 0.80 - 1.39 ) , but a significantly increased risk of prolonged colds ( RR for colds of > 7 vs. 1 - 3 days , 2.53 ; 95 % CI , 1.95 - 3.29 ) . There was no difference in the number of days confined to home . Nonsmoking women passively exposed to cigarette smoke had a slightly increased risk of both more frequent colds ( RR , 1.33 ; 95 % CI , 1.18 - 1.51 ) and more prolonged colds during the previous year ( RR , 1.12 ; 95 % CI , 0.99 - 1.27 ) . CONCLUSIONS Women who are currently heavy smokers are at increased risk of having colds with longer duration compared with nonsmokers . Nonsmoking women passively exposed to cigarette smoking are at slightly increased risk of having more frequent and longer colds than nonsmoking women not exposed to passive smoke AIM To compare clinical , device and biochemical aspects of monotherapy with flixotide vs combination of flixotide with serevent in patients with moderate bronchial asthma ( MBA ) . MATERIAL AND METHODS 18 patients with MBA received flixotide and 18 MBA patients flixotide plus serevent for two weeks of lead-in and eight weeks of basic treatment . A special study was made of neutrophils which were examined for activity of LPO-antioxidants and phospholipid spectrum of membranes . RESULTS There were similar changes in function of the system LPO-antioxidants and lipid structure in neutrophilic membranes of moderate BA patients of both the groups . CONCLUSION Clinicobiochemical efficacy of mean doses of a new topic inhalation glucocorticoid flixotide alone or in combination with prolonged beta 2-adrenostimulator serevent is demonstrated . There were positive trends in metabolic processes in neurophilic membrane . Use of flixotide in combination with serevent is clinical ly preferable OBJECTIVE To examine the effects of nutritional supplement therapy on oxidant-antioxidant status , inflammation and immune system responses , pulmonary function , and health-related quality of life in patients with mild to moderate allergic asthma . METHODS Adult asthma patients ( n=30 ) received daily multiple nutrient supplements for two months . Age- and gender-matched healthy controls ( n=30 ) did not receive any supplements .  Enzymatic and non-enzymatic antioxidant status , malondialdehyde ( MDA ) , high-sensitivity C-reactive protein ( hs-CRP ) , immunoglobulin E ( IgE ) and T-lymphocyte subsets , pulmonary function indices , as well as scores for asthma control and quality of life , were assessed at baseline , at one month of treatment , and at two months of treatment , which was also the end of the study . RESULTS At baseline , asthma patients had significantly higher IgE , MDA , copper ( Cu ) , hs-CRP , and CD19 and CD4/CD8 lymphocyte ratios , and decreased selenium ( Se ) , zinc ( Zn ) , β-carotene , vitamins C and E , and catalase , glutathione peroxidase ( GPx ) and glutathione reductase ( GR ) activities compared to healthy controls ( p < 0.05 ) . During the study period , asthmatics showed non-significantly increased pulmonary function and a trend toward lower IgE levels , markedly reduced MDA , Cu , hs-CRP , and CD19 and CD4/CD8 ratios , and increases in levels of Se , Zn , β-carotene , vitamins C and E , and enzymatic antioxidant activities . Also , their asthma control and health-related quality -of-life scores increased significantly by the end of the study . CONCLUSION Our results indicate that nutritional supplement therapy may improve dysregulated oxidant and antioxidant status , inflammation and immune responses , pulmonary function , and health-related quality of life in patients with mild to moderate allergic asthma In order to study the potential benefit of ascorbic acid in asthma we investigated its role in exercise-induced bronchospasm ( EIB ) . Twelve asthmatic subjects were recruited on the basis of findings compatible with EIB . On two subsequent days the subjects ingested 500 mg . of ascorbic acid or a placebo . The study was performed in a double-blind r and omized fashion . Partial and maximal expiratory flow volume ( PEFV and MEFV ) curves were used to determine pulmonary function changes . Pretreatment with ascorbic acid led to a significant attenuation of the bronchospasm seen five minutes after exercise compared to placebo , as measured by FVC ( 0.23 + /- 0.08 L decrease after ascorbic acid , 0.48 + /- 0.14 L decrease after placebo ) and by FEV1 ( 0.24 + /- 0.06 decrease after ascorbic acid , 0.44 + /- 0.14 decrease after placebo ) Mean + /- SE ) . These results suggest a mild antibronchospastic action of ascorbic acid in subjects with EIB Mild persistent asthma is most effectively controlled with inhaled corticosteroids . Leukotriene receptor antagonists have complementary effects to corticosteroids on inflammation control . The additional effect of a leukotriene receptor antagonist , zafirlukast , was investigated in stable asthma patients under control with inhaled budesonide .  We conducted a r and omised , double-blind , placebo-controlled , single center trial to investigate the effects of add-on zafirlukast treatment to budesonide , on symptom score , pulmonary function , bronchial responsiveness , and serum levels of eosinophilic cationic protein ( ECP ) and antioxidant capacity in stable asthmatic patients under control with inhaled budesonide . The present study included 21 mild or moderate asthmatic patients ( 8 males and 13 females ) , who were stable at least for 6 weeks with inhaled budesonide ( 400 microg/day ) .  Serum total antioxidant capacity ( TAC ) and ECP levels were measured , and symptom scoring , spirometry , and bronchial provocation with methacholine were performed . Then , the patients were r and omised to use either placebo or oral zafirlukast ( 40 mg/day ) in addition to budesonide for 6 weeks . At the 6th week , symptom scoring , spirometry , and bronchial provocation tests were repeated and serum TAC and ECP levels were measured again . After add-on zafirlukast treatment to budesonide , forced expiratory volume in 1 second ( FEV(1 ) ) , TAC and ECP values did not change significantly ( p > 0.05 ) but bronchial hyperresponsiveness and symptom score decreased significantly ( p = 0.022 ) compared to baseline . Thus , in stable asthmatic patients , add-on zafirlukast treatment to budesonide improves symptoms and decreases bronchial hyperresponsiveness BACKGROUND Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear . Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma . A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations . AIMS To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospect i ve multicentre clinical trial to replicate this association . METHODS A total of 300 study participants were included in the analysis .  Dietary soy genistein intake was measured using the Block Soy Foods Screener . The level of  soy genistein intake ( little or no intake , moderate intake , or high intake ) was compared with baseline lung function ( pre-bronchodilator forced expiratory volume in 1 second ( FEV(1 ) ) ) and asthma control ( proportion of participants with an episode of poor asthma control ( EPAC ) and annualised rates of EPACs over a 6-month follow-up period . RESULTS Participants with little or no genistein intake had a lower baseline FEV(1 ) than those with a moderate or high intake ( 2.26 L vs. 2.53 L and 2.47 L , respectively ; p=0.01 ) . EPACs were more common among those with no genistein intake than in those with a moderate or high intake ( 54 % vs. 35 % vs. 40 % , respectively ; p<0.001 ) . These findings remained significant after adjustment for patient demographics and body mass index . CONCLUSIONS In patients with asthma , consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control In this study , prospect ively , we aim ed to determine the effects of the different treatment alternatives on the oxidant system and inflammatory and clinic determinants during the stable period of 1 month following an asthmatic attack . Thirty‐one patients ( 22 female , nine male ) were r and omly divided into three groups following the stabilization of an acute asthma attack . The control group that is an additional group to the three patient groups consisted of 10 healthy volunteers ( five female , five male ) . The following protocol s were used for 4 weeks : Group I : short‐acting inhaler β2 mimetic as required ( treatment A)+800 μg inhaler budesonide ( treatment B)+leukotriene receptor antagonist ; Group II : treatment A and B ; Group III : treatment A and B+vitamin E.  The serum levels before and after treatment of eosinophilic cationic protein ( ECP ) , leukotriene E4 ( LTE4 ) , and malondialdehyde ( MDA ) were determined . The values before and after treatment were statistically compared both with each other and control values . Pretreatment ECP , LTE4 , and MDA levels for the three groups were significantly higher compared with post‐treatment levels ( P<0.05 to P<0.001 ) and the control levels ( P<0.01 to P<0.001 ) . However , when post‐treatment levels were compared with those of the control group , no significant differences were found ( P>0.05 ) . Lack of significant variation was observed when the pre‐ and post‐treatment differences in the three groups were compared for each one of ECP , LTE4 , and MDA levels ( P>0.05 ) . Leukotriene receptor antagonist or antioxidant agents added to st and ard asthma treatment did not make a significant contribution on ECP , LTE4 , and MDA levels and respiratory parameters such as spirometric function tests . Etiologic factors and /or the possible changes in different pathogenetic ways of the inflammation process may have been responsible for nonsignificant intertreatment difference in the biomarker levels . The result confirms that suppressing the inflammation in asthma enables the entire inflammatory pathologic process to be controlled BACKGROUND It has been suggested that exercise-induced bronchoconstriction may involve oxidative stress . Strenuous exercise promotes free radical production , which can lead to many of the pathophysiologic changes associated with asthma , including bronchoconstriction , mucus secretion , and microvascular leakage . Lycopene has been shown to have high antioxidative activity . OBJECTIVE To evaluate the effect of lycopene supplementation on airway hyperreactivity and inflammation in young athletes who complain of difficulty in breathing related to physical exertion . METHODS Nineteen young athletes with exercise-related difficulty in breathing visited the exercise laboratory 3 times . During the first visit , participants underwent a baseline evaluation of exercise-induced bronchoconstriction . Daily for 1 week before each of the 2 subsequent visits , participants ingested 30 mg of lycopene ( a natural antioxidant ) or placebo ( in r and omized order , double-blind ) . A 2-week washout period was given between each visit . During each visit , lung functions were evaluated before and after an 8-minute run on the treadmill ( 85 % of the predicted maximal heart rate ) . RESULTS There was no difference in the mean+/-SD decrease in forced expiratory volume in 1 second after exercise during lycopene treatment compared with placebo treatment ( 11.8%+/-12.5 % and 11.0%+/-11.6 % ) . In addition , there was no apparent division into responders and nonresponders . CONCLUSION A daily dose of lycopene for 1 week does not affect lung function after exercise and may not provide any protective effect against clinical difficulty in breathing in young athletes Objective : We report on the effect of glutathione , an antioxidant compound on the airway response to the ultrasonically nebulised distilled water ( UNDW , ‘ fog ’ ) challenge . Methods : 12 subjects with mild-to-moderate bronchial asthma underwent double-blind , cross-over pretreatment , administered 30 min earlier , in a r and omised order with inhaled glutathione ( G ) ( 600 mg ) , sodium cromoglycate ( SCG ) ( 20 mg ) and placebo ( P ) , followed by the challenge . Results : After P pretreatment UNDW challenge caused a mean 20.41 % decrease in FEV-1 ( p < 0.05 ) , after G , a mean 6.04 % fall in FEV-1 ( p = n.s . ) , and after SCG a mean 5.99 % fall in FEV-1 ( p = n.s . ) . Conclusions : G significantly attenuated ‘ fog’-induced falls in FEV-1 ( p < 0.001 compared with P ) and showed a protective effect on UNDW-induced bronchoconstriction AIM The study aims to assess the a priori hypothesis that regular supplementation with vitamin C or magnesium will permit a reduction in the corticosteroid dose required to maintain asthma control in adults . METHODS We invited all participants recruited from primary care centres who completed a parallel-group , r and omised , placebo-controlled  , 16-week supplementation trial of 1g/day vitamin C or 450 mg/day magnesium to continue and participate in a structured corticosteroid reduction protocol over 10 weeks . RESULTS A total of 92 participants ( 29 vitamin C , 31 magnesium and 32 placebo ) entered the study . Assuming no reduction in corticosteroid dose in the 10 who subsequently withdrew , the geometric mean reductions in inhaled corticosteroid dose achieved with vitamin C , magnesium and placebo were 49 , 13 and 11 microg , respectively . Relative to placebo , the unadjusted effect of vitamin C was significant , and remained at borderline significance after adjustment for baseline corticosteroid dose ( relative reduction ratio=4.03 , 95 % CI 0.95 to 17.1 , P=0.06 ) . CONCLUSIONS We conclude that while vitamin C supplements may have modest corticosteroid sparing effects and hence the potential to reduce exposure to their side effects , magnesium supplements have no effect on the inhaled corticosteroid dose required to maintain asthma control BACKGROUND Glutathione is central to the antioxidant defences of the lung . The aim of this study was to determine whether sputum induction can be used for the measurement of glutathione in the respiratory tract . METHODS Saliva and induced sputum ( 3 % NaCl , 20 minutes ) sample s were collected from 10 healthy individuals and 10 patients with stable asthma receiving treatment with inhaled corticosteroids .  Sample s were chilled on ice and dispersed by dilution with ice cold phosphate buffered saline and pipetting . Cell-free supernatants were obtained by centrifugation of sample s and filtration of supernatants and analysed for total glutathione , glutathione disulfide , and albumin content . The cells were treated with dithiothreitol and cell numbers , cell viability , and differential cell patterns were determined . RESULTS As judged by cell viability and percentage of non-squamous cells , adequate sputum sample s were obtained from nine healthy and nine asthmatic subjects . The salivary total glutathione content was low ( median concentration 1.2 μM ( range 0.8–1.5 ) in healthy subjects and 0.9 μM ( 0.7–1.2 ) in asthmatic subjects ) . The sputum total glutathione content of both healthy and asthmatic subjects was within the same range ( 3.9 ( 1.0–12.3 ) μM and 6.4 ( 1.3–19.2 ) μM , respectively ; p=0.35 ) . Surprisingly , and in marked contrast to results obtained with bronchoalveolar lavage , sputum levels of glutathione disulfide represented more than 50 % of the total glutathione in both groups ( 50.9 % ( range 24.6–83.1 ) and 72.3 % ( range 36.5–97.4 ) , respectively ; p=0.2 ) . CONCLUSIONS The results of this study indicate that sputum induction can be used to measure the glutathione content of bronchial secretions . Sputum glutathione levels of stable asthmatic patients did not differ significantly from healthy controls Apocynin is an inhibitor of NADPH oxidase present in inflammatory cells such as eosinophils and neutrophils . We investigated the effect of inhaled apocynin on ozone-induced bronchial hyperresponsiveness in vivo . Seven mild atopic asthmatics participated in a placebo-controlled , cross-over study with two exposures to O(3 ) at 2-week intervals . Apocynin ( 3 ml of 0.5 mg/ml ) was inhaled 2 times before and 6 times after O(3 ) exposure at hourly intervals . At 36 h before and 16 h after O(3 ) exposure , methacholine inhalation challenge tests ( Mch ) were performed , and PC(20 ) and maximal % fall from baseline ( MFEV(1 ) ) were calculated from dose-response curves . O(3)-induced change in PC(20 ) ( Delta PC(20 ) ) after placebo treatment was -1.94 + /- 0.39 DD ( mean + /- SEM doubling dose Mch ) ( p = .001 ) and apocynin was -0.6 + /- 0.33 DD ( p = .17 ) . The difference between apocynin and placebo treatment was 1.3 DD + /- 0.42 ( p = .02 ) . O(3)-induced Delta MFEV(1 ) was 11.9 + /- 1.5 % ( p = .008 ) during placebo inhalation and 3.85 + /- 1.8 % during apocynin ( p = .47 ) . Apocynin reduced the Delta MFEV(1 ) by 8.05 % compared to placebo ( p = .025 ) . We conclude that apocynin markedly reduced O(3)-induced hyperreactivity for Mch as well as maximal airway narrowing . The results suggest that apocynin may have a role in preventing ozone-induced exacerbations of asthma UNLABELLED The aim of study was to analyze the effect of treatment with inhaled corticosteroids and long acting beta2-agonists on antioxidative-prooxidative balance in children with asthma . MATERIAL S AND METHODS Twenty children with newly diagnosed asthma before treatment ( group 1 ) , fourteen children with diagnosed asthma treated with inhaled corticosteroids and long acting beta2-agonists and 57 healthy children were ioncluded in the study . In all cases plasma protein carbonyls and activity of erythrocyte SOD was assayed . RESULTS Plasma protein carbonyls in both group I ( 1,01 nmol/g of protein , SD=0,30 ) and group II ( 0,94 ; SD=0,15 ) was significantly higher than in group III ( 0,85 ; SD=0,24 ) ( I vs III p<0,033 ; II vs III p<0,031 ) . The highest SOD activity was found in group II ( 3156,4 U/gHb ; SD=976,1 ) ( II vs I p<0,02 ; II vs III p<0,0001 ) . SOD activity n group I ( 2435,8 , SD=730,2 ) was higher than in group III ( 1533,1 , SD=703,8 ) ( p<0,0001 ) . CONCLUSIONS The increase in SOD activity in children with asthma seems to be a response to intensification of oxidative stress . Treatment of asthma with inhaled corticosteroids and long acting beta2-agonists augments antioxidative defense by increase in superoxide dismutase activity We investigated the effect of theophylline administration on circulating vitamin levels in children with asthma . Twenty-three asthmatic children , ranging in age from 7 to 15 with a mean of 10.8 years and including 16 patients who were treated with slow-release theophylline and 7 patients not receiving any type of theophylline preparation , were enrolled in this study . They all were in patients who had been hospitalized for the control of asthma .  Steady-state serum theophylline and vitamin A , B1 , B2 , B6 , B12 and C levels were evaluated in these patients . Circulating vitamin B1 and B6 levels were depressed in asthmatic children treated with theophylline compared to those not receiving the agent ( 38.4 + /- 1.6 ( mean + /- SEM ) vs. 46.4 + /- 3.5 ng/ml and 7.1 + /- 0.5 vs. 11.8 + /- 2.1 ng/ml , respectively , p < 0.05 ) . A significant negative correlation between theophylline and circulating levels of vitamin B6 was demonstrated in the subjects of this study ( rs = -0.657 , p < 0.001 ) . In contrast , no relationship was noted between theophylline and circulating vitamin B1 levels . Theophylline did not affect circulating vitamin A , B2 , B12 or C levels . We conclude that theophylline induces depression of circulating vitamin B1 and B6 levels in asthmatic children , although a dose-dependent interaction between theophylline and vitamin B1 would be unlikely
BACKGROUND Dietary antioxidants , such as vitamin C , in the epithelial lining and lining fluids of the lung may be beneficial in the reduction of oxidative damage ( Arab 2002 ) .
They may therefore be of benefit in reducing symptoms of inflammatory airway conditions such as asthma , and may also be beneficial in reducing exercise-induced bronchoconstriction , which is a well-recognised feature of asthma and is considered a marker of airways inflammation .
However , the association between dietary antioxidants and asthma severity or exercise-induced bronchoconstriction is not fully understood .