Serum but not exhaled breath condensate periostin level is increased in competitive athletes.

INTRODUCTION: Periostin is a matricellular protein expressed by many tissues. Its release may be enhanced, among others, through mechanical stimulation of muscles and bones as well as by cytokines of allergic inflammation. OBJECTIVES: Our aim was to assess periostin levels in serum and exhaled breath condensate (EBC) of professional athletes, asthmatics and healthy controls. We also sought to determine whether acute treadmill exercise influences serum and EBC periostin. METHODS: Study groups included 9 competitive swimmers, 10 mild-to-moderate asthmatics and 7 healthy controls. Athletes were assessed twice (in- and off-training period) while asthmatics and controls in one time-point. Data on demographics, allergy symptoms and exercise load were acquired through Allergy Questionnaire for Athletes (AQUA) and International Physical Activity Questionnaire (IPAQ). Serum and EBC were collected before and after treadmill exercise challenge. RESULTS: Baseline serum periostin in swimmers during training period was significantly higher (5- to 7-fold) than in asthmatics (P = .01) and controls (P < .05). In EBC, lowest periostin levels were seen in athletes in-training as compared with off-training period (P < .01) and with asthmatics (P < .03). Acute bout of exercise did not induce significant changes neither in serum nor in EBC periostin in any group. CONCLUSION: Increased serum, but not EBC, periostin levels in competitive athletes are probably because of permanently increased exercise load leading to stimulation, injury and regeneration of musculoskeletal tissues. Periostin may be considered marker of long-term exercise overload after confirmation in larger groups.

Serum tryptase level and inflammatory markers in exhaled breath condensate of children with exercise-induced symptoms.

BACKGROUND: The pathogenesis of exercise-induced bronchoconstriction (EIB) is poorly understood. OBJECTIVE: To evaluate the biomarkers concentration in exhaled breath condensate (EBC) in schoolchildren with postexercise symptoms. We also evaluated changes in fractional exhaled nitric oxide (FeNO) value and the serum tryptase level after exercise. METHODS: One hundred children with postexercise symptoms were included. Methacholine challenge testing (MCT) was performed at visit 2, and exercise challenge testing (ECT) was performed at visit 3. Before and after ECT serum tryptase levels and FeNO values were measured. EBC was collected after ECT from 10 randomly selected children from each group. The children were assigned to the following groups: ECT(+) MCT(+), ECT(+) MCT(-), ECT(-) MCT(+), ECT(-) MC(-). We measured the following molecules: eotaxin, interleukin (IL) 8, IL-1ra, IL-1 beta, IL-6, IL-1 alpha, IL-12(p40), IL-5, granulocyte-macrophage colony-stimulating factor, IL-7, IL-15, IL-4, IL-2, IL-10, tumor necrosis factor alpha, interferon gamma, IL-13, tumor necrosis factor beta, monocyte chemoattractant protein-1, IL-17A, macrophage inflammatory proteins-1 alpha, macrophage inflammatory proteins-1 beta, IL-12(p70), and regulated on activation, normal T-cell expressed and secreted by using a multiplex immunoassay. Prostaglandin E2 (PGE2), leukotriene B4, and cysteinyl leukotriene were analyzed by using separate enzyme-linked immunosorbent assay kits. RESULTS: In the MCT(+) group, a detectable level of IL4 in EBC and detectible levels of eicosanoids were seen in the ECT(+) group. We observed the opposite direction of ECT-induced changes in FeNO and serum tryptase concentrations in patients with detectable compared with patients without detectable levels of cytokines in EBC. We showed ECT-induced reduction in the tryptase level in patients with a nondetectable PGE2 level in EBC and an increase in tryptase levels in patients who had detectable levels of PGE2 in EBC. CONCLUSIONS: EBC was a useful method to estimate inflammation but only in children with symptoms and with EIB shown by a positive ECT. Children with a positive ECT had detectable levels of eicosanoids in EBC; the opposite direction of ECT-induced changes in FeNO and serum tryptase concentrations was observed. The results of above study confirm the role of mast cells and eicosanoids in the pathogenesis of EIB in children.

Reduction in the leptin concentration as a predictor of improvement in lung function in obese adolescents.

OBJECTIVE: To assess the effects of weight loss on adipokines, asthma-related symptoms, exercise-induced bronchospasm (EIB) and lung function, and to evaluate the role of leptin and adiponectin levels on lung function after treatment in obese adolescents. METHODS: 84 postpubertal obese adolescents were enrolled and distributed in quartiles according to weight loss (low (<2.5 kg), low to moderate (>2.5 and <8 kg), moderate (<8 and <14 kg) and massive (<14 kg)). Body composition was measured by plethysmography, and visceral and subcutaneous fat were detected by ultrasound. Serum levels of adiponectin and leptin were analyzed. Lung function, asthma and EIB were evaluated according to the American Thoracic Society criteria. Patients were submitted to 1 year of interdisciplinary intervention consisting of physiotherapy, medical, nutritional, exercise, and psychological therapy. RESULTS: After treatment the moderate and massive weight loss promoted an increase in adiponectin and adiponectin/leptin (A/L) ratio as well as a decrease in leptin levels and a reduction in EIB frequency and asthma-related symptoms. Furthermore, the reduction in leptin levels was a predictor factor to improvement in lung function. CONCLUSION: Interdisciplinary therapy was able to decrease EIB and asthma-related symptoms and to improve pro/anti-inflammatory adipokines. Additionally, the leptin concentration was a predictor factor to explain changes in lung function.

Serum leptin and adiponectin levels correlate with exercise-induced bronchoconstriction in children with asthma.

BACKGROUND: Exercise-induced bronchoconstriction (EIB), a form of bronchial hyperresponsiveness (BHR), is common in children with asthma or obesity. Epidemiological studies have shown that asthma and obesity are increasing in parallel, but obesity- and adipokine-related effects on inflammation and BHR have not yet been demonstrated in the human airway. OBJECTIVE: To address the relationship between leptin and adiponectin and EIB in children with asthma. METHODS: Eighty-five prepubertal children between the ages of 6 and 10 years were included in our study. They comprised obese with asthma (n = 19), normal weight with asthma (n = 23), obese without asthma (n = 23), and healthy (n = 20). We measured serum leptin and adiponectin levels. We also performed pulmonary function tests: baseline, postbronchodilator inhalation, methacholine inhalation, and exercise. The area under the forced expiratory volume in 1 second (FEV(1))-time curve quantified the severity of EIB over a 20-minute period after exercise (AUC(20)). RESULTS: The obese children had significantly elevated levels of leptin and reduced levels of adiponectin. The maximum decreases in %FEV(1) and AUC(20) after exercise were positively correlated with leptin levels and negatively with serum adiponectin levels in children with asthma. The odds for having EIB were incrementally and significantly higher for children with higher levels of serum leptin. CONCLUSIONS: Levels of the adipocyte-derived hormones leptin and adiponectin are significantly correlated with BHR induced by exercise challenge in children with asthma. Further studies are needed to elucidate whether the changes in leptin and adiponectin levels bear a causal relationship to the EIB/BHR.

Serum vitamin D levels and exercise-induced bronchoconstriction in children with asthma.

Epidemiological studies have established a relationship between low levels of serum vitamin D and reduced lung function in healthy adults, and asthma onset and severity in children. However, no study has examined the relationship between vitamin D levels and exercise-induced bronchoconstriction in asthmatic children. We evaluated the relationship between 25-hydroxyvitamin D concentrations and baseline forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and change in FEV1 (ΔFEV1) after a standardised exercise challenge in 45 children with intermittent asthma. Only 11% of the children had desirable serum vitamin D levels (at least 30-40 ng·mL(-1)). A positive correlation was found between serum 25-hydroxyvitamin D and both FVC (r=0.34; p=0.037) and FEV1 (r=0.32; p=0.037). Subjects with a positive response to the exercise challenge (ΔFEV1≥10%) presented lower serum levels of 25-hydroxyvitamin D than children with a negative challenge (mean±sd 16.2±5.2 versus 23.4±7.0 ng·mL(-1), respectively; p=0.001). Our results indicate that hypovitaminosis D is frequent in asthmatic children who live in a Mediterranean country. In those children, lower levels of vitamin D are associated with reduced lung function and increased reactivity to exercise.

Wheat-dependent, exercise-induced anaphylaxis in Thai children: a report of 5 cases.

Wheat is not an uncommon cause of food-dependent, exercise-induced anaphylaxis. This study aims to describe common clinical characteristics and laboratory manifestations of the disease. Five children, aged 8-14 years were evaluated. An atopic history was found in 20% of the patients. All patients had symptoms which involved the skin and three had hypotension. Serum specific IgE for wheat was measured and showed a positive result in 2 patients. A three-day challenge protocol with an open challenge for wheat on day 1, an exercise challenge test on day 2 and another exercise challenge test on day 3 after a meal containing wheat was performed. Four patients completed the three-day challenge protocol. Anaphylaxis occurred in 2 out of 4 patients who consumed more than 100 grams of wheat prior to the exercise. The three-day challenge protocol is a definitive diagnostic tool to confirm the diagnosis of WDEIA. However, the amount of wheat used for challenging should be at least 100 grams.

Wheat allergy.

PURPOSE OF REVIEW: This review describes the diverse clinical manifestations of IgE-mediated allergy to ingested wheat and summarizes recent advances in characterization of clinically significant allergens and diagnostic workup. RECENT FINDINGS: Recent population-based studies have shown the prevalence of wheat allergy and sensitization more precisely than past studies among small populations and in hospital settings. Intensive research has demonstrated the diverse profile of both water/salt-soluble and insoluble allergens involved in clinical types of wheat allergies determined depending on the patient age, the sensitization route, and the protein state during the exposure. Consequently, some new allergens, including nonspecific lipid transfer protein (Tri a 14), have been identified. For diagnosis, the role of water/salt-insoluble gliadins, particularly omega-5 gliadin, a major allergen of wheat-dependent, exercise-induced anaphylaxis, was assessed as compared with the results of oral challenges. The mechanisms of eliciting anaphylactic symptoms by exercise in wheat-dependent, exercise-induced anaphylaxis were speculated upon; one is the allergenicity strengthened by activated tissue transglutaminase and another is the increased absorption of allergens through the gastrointestinal tract. SUMMARY: Findings of the recent studies show potential for more precise diagnosis in each clinical type of wheat allergies.

Association of IL-13 polymorphisms with leukotriene receptor antagonist drug responsiveness in Korean children with exercise-induced bronchoconstriction.

BACKGROUND: IL-13 is a pivotal cytokine in allergic inflammation and bronchial hyperresponsiveness, and is known to influence leukotriene levels. OBJECTIVE: We investigated whether IL-13 polymorphisms may be associated with clinical phenotypes and drug responsiveness to the leukotriene receptor antagonist (LTRA) in Korean asthmatic children with exercise-induced bronchoconstriction (EIB). METHODS: We enrolled 242 normal controls and 374 patients with asthma. Of the asthmatic patients, 100 performed exercise challenge tests before and after receiving montelukast (5 mg/day) for 8 weeks and included 80 subjects in drug responsiveness analysis. We assessed IL-13 polymorphisms (-1512A/C, -1112C/T, +2044G/A) through PCR-restriction fragment length polymorphism analysis. RESULTS: Significantly higher total IgE levels and maximum percent fall in forced expiratory volume in 1 s (FEV1) (%) after exercise challenge test were found in asthmatic patients carrying one or two copies of the IL-13 +2044A versus those homozygous for +2044G (P=0.011 and 0.040, respectively). We further noted a correlation of total IgE with maximum percent fall in FEV1 (%) in asthmatic patients, as well as a reverse correlation with improvement of maximum percent fall in FEV1 (%) after exercise challenge tests. Finally, we observed a significant association between responsiveness to montelukast and IL-13 -1112C/T polymorphism and the haplotype of IL-13 polymorphisms. CONCLUSION: The IL-13 +2044G/A polymorphism may be associated with atopy and EIB severity in Korean children with EIB, and thus could potentially be considered as a disease-modifying gene. Moreover, the IL-13 -1112C/T polymorphism and the haplotype of IL-13 polymorphisms seem to be associated with LTRA drug responsiveness, and thus might prove useful as a target for modulation of LTRA drug responsiveness.

The role of lipoxin A4 in exercise-induced bronchoconstriction in asthma.

BACKGROUND: The pathogenesis of exercise-induced bronchoconstriction in asthma is incompletely understood, and the role of lipoxin A4 has not been investigated. OBJECTIVE: To investigate the involvement of lipoxin A4 in exercise-induced bronchoconstriction. METHODS: Two groups of children were enrolled in the study: asthmatic children with positive (n = 12) and negative (n = 8) responses to exercise. Levels of lipoxin A4 were determined in plasma before and immediately after exercise challenge using enzyme-linked immunosorbent assay. RESULTS: No significant difference was observed in the pre-exercise lipoxin A4 levels among the groups (p > 0.05). A significant difference was observed in the postexercise lipoxin A4 levels between the two groups (p = 0.041). We also observed significant decreases in plasma lipoxin A4 levels immediately after exercise challenge both in asthmatic children with positive responses to exercise (p = 0.013) and negative responses to exercise (p = 0.05). But these levels were significantly higher in asthmatic children with negative responses to exercise (p = 0.041). There was an inverse correlation between lipoxin A4 levels and a reduction in forced expiratory volume at one second percent after exercise (p = 0.045, r = -0.465). CONCLUSION: Our results are the first demonstration of the lower levels of lipoxin A4 associated with exercise-induced bronchoconstriction in asthma. We hypothesize that the development of exercise-induced bronchoconstriction in asthmatic children may be in relation to a reduced endogenous lipoxin biosynthetic capability. Lipoxin mimetics and related compounds could provide novel therapeutic approaches to the treatment of exercise-induced bronchoconstriction in asthma.

Adenosine level in exhaled breath increases during exercise-induced bronchoconstriction.

In asthmatic patients, airway obstruction provoked by exercise challenge is accompanied by an increase in plasma adenosine level. In this study, the current authors investigated if exercise-induced bronchoconstriction was associated with local changes of adenosine concentration in the airways. Oral exhaled breath condensate (EBC) collection (5-min duration) and forced expiratory volume in one second (FEV1) measurements were performed at rest (baseline) and 4-8 times after treadmill exercise challenge in healthy and asthmatic subjects. Adenosine concentration in EBC was determined by HPLC. Observations indicated that physical exercise results in bronchoconstriction together with a significant increase of adenosine level in EBC in asthmatic patients (mean+/-sd maximal fall in FEV1 27+/-13%; associated increase in adenosine 110+/-76% as compared to baseline), but not in healthy control subjects. Exercise-induced changes in adenosine concentration correlated significantly with the fall in FEV1 values in asthmatic patients. In conclusion, the observed increase in adenosine concentration of oral exhaled breath condensate most probably reflects changes in the airways during exercise-induced bronchoconstriction. Due to its known bronchoconstrictor property in asthma, adenosine may contribute to the development of bronchospasm.

Changes in blood levels of eosinophil cationic protein and tryptase after exercise challenge in adolescents with exercise-induced asthma.

BACKGROUND: Exercise-induced asthma (EIA) is increasingly encountered among school children in Kuwait. Available evidence has shown that inflammatory mediators may be involved in the pathogenesis of EIA. Studies on release of inflammatory mediators have been carried out in adult patients with asthma in Kuwait, but no study on EIA involving children has taken place in this region. OBJECTIVE: To investigate changes in the concentration of some of the mediators involved in EIA in adolescent school children, using exercise challenge. DESIGN: Prospective, case control study. SETTING: Respiratory and Cardiology units Mubarak Hospital, Kuwait, between January and June 2001. SUBJECTS: Nine EIA and 14 non-EIA and 10 normal control subjects, designated as groups one, two and three aged between 13 and 17 years, who were non-smokers, were enrolled for the study. MAIN OUTCOME MEASURES: Blood eosinophils (EOS), eosinophil cationic protein (ECP) and tryptase were estimated pre-exercise, 5 and 30 minutes after exercise. Spirometry was measured at the same period. RESULTS: In group one, ECP and tryptase levels fell after exercise, but significant difference in the levels were obtained only in tryptase between pre-exercise and 30 minutes after exercise (4.1 microg/L Vs 3.8 microg/L) P <0.05, while the difference for ECP was not significant (P=0.09). In group two, both tryptase (6.0 microg/L Vs 5.7 microg/L) P < 0.05, and ECP (21.8 microg/L Vs 12.1 microg/L) P<0.01, fell after exercise. However, in group three, no appreciable difference was observed between pre and post exercise. Correlation between tryptase and EOS (r=0.770; P<0.05) and between tryptase and ECP (r=0.850; p<0.05) was observed pre-exercise and after exercise in groups one and two. CONCLUSION: A fall in the level of the mediators was observed after exercise challenge, but the relevance of this finding in the pathogenesis of EIA remains unclear. Further studies are required to verify this finding.

[Influence of physical effort on concentration of lactic acid and acid-base equilibrium in patients with mild and moderate bronchial asthma]. / Wplyw wysilku fizycznego na stezenie kwasu mlekowego i równowage kwasowo-zasadowa u chorych na astme oskrzelowa lekka i umiarkowana.

PURPOSE: Estimate influences of standard physical exercise on lactic acid concentration and acid-base equilibrium in patients with mild and moderate bronchial asthma compared with healthy trained persons and do not ones. MATERIAL AND METHODS: In 47 asthmatic patients and 20 healthy persons: 1) bronchial reactivity was investigated; 2) at rest and 1, 5 and 10 min after 8 min exercise (PWC85%max, bicycle ergometer): FEV1, lactic acid concentration (LAC), pH, pO2, pCO2 and HCO3 (in capillary blood) were investigated. Among asthmatic patients: 1) 21 experienced exercise-induced asthma (EIA), 2) 20 reacted to histamine in concentration of 0.125 mg/ml/3', 3) 6 reacted to histamine in concentration of 0.25 mg/ml/3'. In healthy persons, without EIA and reaction to histamine, were: 12 who did not train, and 8 athletes. RESULTS: After exercise LAC increased in all groups (p<0.05); the increase was significantly higher in patients and persons who did not train, then athletes, and did not normalised, in opposite to athletes, however in persons who did not train was significantly lower then in asthmatics. pH and pCO2 did not change significantly in all examined persons, but HCO3 decreased significantly in patients with bronchial hyperactivity and in persons who did not train. Significant increase of pO2 appeared only in healthy persons. CONCLUSION: Physical effort caused significant greater metabolic changes in asthmatic patients then in healthy persons, especially athletes

[A study on the role of T lymphocytes and eosinophil cationic protein in exercise-induced asthma].

OBJECTIVE: To explore the role of eosinophil cationic protein (ECP) and T lymphocytes in exercise-induced asthma (EIA). METHODS: In 32 patients with asthma (13 patients with EIA) and 8 normal subjects, peripheral blood ECP, CD(25)(+)%, and IL-5 mRNA were measured before, 10 min and 60 min after exercise testing. RESULTS: (1) There was a linear relationship between ECP, CD(25)(+)% and the forced expiratory volume in one second (FEV(1)) before exercise (r = -0.79, -0.61, P < 0.01). (2) In patients with EIA, FEV(1) and PEF decreased remarkably after exercise test, but in patients without EIA, FEV(1) and PEF did not change. The difference between the two groups was significant. (3) There was no significant difference between the two groups in terms of ECP, CD(25)(+)%, and IL-5 mRNA. CONCLUSION: T lymphocyte activation and ECP secreted by eosinophils do not seem to play a major role in EIA.

[Measurement of cytokines in patients with exercise-induced asthma treated with anti-leukotrienes]. / Determinación de citocinas en pacientes con asma inducida por el ejercicio y tratada con un antileucotrieno.

BACKGROUND: Exercise-induced asthma is defined as the transient broncho-spasm, that occurs after 3 to 8 minutes of continuous exercise; one of two mechanisms are implicated: the first is given by a hyper-osmolar environment interchange with the warm respiratory air and the water loss, the second due to reactive hyperemia or bronchial blood vessels edema. OBJECTIVES: To determine the effectiveness and safety of Zafirlukast treatment in exercise induce asthma, and in mild and moderated persistent bronchial asthma. Evaluate the security with laboratory test IL-2, IL-4, INFg, and CD69, to determinate TH1 and Th2 cells, laboratory and thorax x-ray determinations before and after zafirlukast treatment in exercise induce asthma, plus the functional respiratory test, and assert the clinical and adverse reaction with Zafirlukast. MATERIAL AND METHODS: A open, prospective, longitudinal study. Challenge test on a treadmill for 8 minutes. Twenty patients from the Allergy Service at Lic. Adolfo López Mateos Hospital, ISSSTE, in México City, fifteen female and five males. Aged 15 to 35 years. There was a control group of ten healthy subjects with similar age and sex. The drug Zafirlukast was administered 20 mg twice a day for eight weeks, with patient's informed and signed consent. Laboratory test: Blood Cell count, transaminases, bilirubins A, G, M and E immunoglobulins thorax X-ray, electrocardiogram, functional respiratory test before and after treatment. RESULTS: Zafirlukast blocked exercise induced asthma in the early and late phases. There was a statistically significant improvement of a VEF-1 after exercise with a p > 0.001; furthermore, there was significant improvement in the mid-spiratory speed before the exercise with a p > 0.05. The mid-spiratory speed after the exercise, improved (p > 0.01). There were no collateral reactions, such as Churg-Strauss, only transitory headache in six and nauseas in two. There were no statistically significant changes in the cytokines assessment. CONCLUSIONS: There were no statistically significant changes in the cytokines assessments, in four cases the IL-4 decreased after the treatment. The anti-leukotriene improved the bronchospastic answer during the early and late phases, reducing the FEV-1, decreasing the recovering phase.

Plasma adenosine concentration increases during exercise: a possible contributing factor in exercise-induced bronchoconstriction in asthma.

We investigated whether the level of plasma adenosine (ADO) changed during exercise and whether this could be related to exercise-induced bronchoconstriction. Baseline levels of ADO did not differ, but exercise resulted in higher ADO in patients with asthma than in healthy subjects (86 +/- 35 vs 59 +/- 16 nmol/L; P <.001). In patients with asthma, the increase in ADO was related to decreases in FEV(1) (r (2) = 0.475; P <.05) and SaO(2) (r (2) = 0.693; P <.05). These data suggest that adenosine might be involved in the development of exercise-induced bronchoconstriction.

Blood eosinophil counts for the prediction of the severity of exercise-induced bronchospasm in asthma.

It has been suggested that airway eosinophilic inflammation is associated with the severity of exercise-induced bronchospasm (EIB). Blood eosinophils are known to be an indirect marker of airway inflammation in asthma. The aim of this study is to investigate that a simple and easy blood test for blood eosinphil counts may predict the severity of EIB in asthma. Seventy-seven men with perennial asthma (age range 18-23 years) were included. Lung function test, skin prick test, and blood tests for eosinophils counts and total IgE levels were performed. Methacholine bronchial provocation test and, 24 h later, free running test were carried out. EIB was defined as a 15% reduction or more in post-exercise FEV1 compared with pre-exercise FEV1 value. Atopy score was defined as a sum of mean wheal diameters to allergens. EIB was observed in 60 (78%) of 77 subjects. Asthmatics with EIB showed significantly increased percentages of eosinophils (P<0.01), log eosinophil counts (P<0.001), and atopy scores (P<0.05) and decreased log PC20 values (P < 0.05) compared with asthmatics without EIB. Asthmatics with eosinophils of > 700 microl(-1) (36.9 +/- 12.7%) had significantly greater maximal % fall in FEV1 after exercise than asthmatics with eosinophils of < 350 microl(-1) (24.7 +/- 16.6%, P <0.05). Blood eosinophil counts > 350 microl(-1) yielded the specificity of 88% and positive predictive value of 93% for the presence of EIB. When a multiple regression analysis of maximal % fall in FEV1 according to log eosinophil counts, log PC20, log IgE and atopy score was performed, only blood eosinophil counts were significant factor contributing to the maximal % fall in FEV1 after exercise. These findings not only suggest that a simple blood test for eosinophils may be useful in the prediction of the severity of EIB, but also reinforce the view that airway eosinophilic inflammation may play a major role in EIB in asthma.

The new phosphodiesterase 4 inhibitor roflumilast is efficacious in exercise-induced asthma and leads to suppression of LPS-stimulated TNF-alpha ex vivo.

Roflumilast is a new phosphodiesterase 4 (PDE4) inhibitor developed by Byk Gulden Pharmaceuticals for the treatment of chronic obstructive pulmonary disease and asthma. A placebo-controlled, randomized, double-blind, two-period crossover study was performed to investigate the safety and efficacy of roflumilast in 16 patients with exercise-induced asthma. The patients received placebo or roflumilast (500 microg/day) for 28 days, each according to the randomly determined treatment sequences roflumilast/placebo and placebo/roflumilast. In both study periods, exercise challenge was performed 1 hour after dosing on days 1, 14, and 28. FEV1 was measured before exercise challenge, immediately after the end of exercise challenge, and then at 1, 3, 5, 7, 9, and 12 minutes after the end of challenge. Blood samples for the determination of lipopolysaccharide (LPS)-stimulated tumor necrosis factor alpha (TNF-alpha) in whole blood ex vivo as a surrogate marker for the inhibition of inflammatory cell activation were taken predose on days 1 and 28. Serial safety measurements were performed during both study periods. Analysis of variance for the crossover design showed a significant superiority of roflumilast over placebo on day 28. The mean percentage fall of FEV1 after exercise was reduced by 41% as compared to placebo (p = 0.021). An improvement of lung function during roflumilast treatment was also observed on days 1 and 14. The median TNF-alpha level decreased by 21% (p = 0.009) during roflumilast treatment but remained essentially constant under placebo. It is concluded that roflumilast is effective in the treatment of exercise-induced asthma. This result was accompanied by a significant reduction of TNF-alpha levels ex vivo. Treatment with roflumilast was safe and well tolerated.

Reduction of exercise-induced asthma oxidative stress by lycopene, a natural antioxidant.

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-MATO) on airway hyperreactivity were assessed in patients with exercise-induced asthma (EIA). METHODS: Twenty patients with EIA participated in our study to verify the antioxidative effects. The test was based on the following sequence: measurement of baseline pulmonary function, 7-min exercise session on a motorized treadmill, 8-min rest and again measurement of pulmonary function, 1-week, oral, randomly administered, double-blind supplementation of placebo or 30 mg/day of lycopene (LYC-O-MATO), measurement of pulmonary function at rest, 7-min exercise session, and 8-min rest and again measurement of pulmonary function. A 4-week washout interval was allowed between each protocol. RESULTS: All patients given placebo showed significant postexercise reduction of more than 15% in their forced expiratory volume in 1 s (FEV1). After receiving a daily dose of 30 mg of lycopene for 1 week, 11 (55%) patients were significantly protected against EIA. Serum analyses of the patients by high-pressure liquid chromatography detected in the lycopene-supplemented patients an elevated level of lycopene compared to the placebo group, with no change in retinol, tocopherols, or in the other carotenoids. CONCLUSIONS: Our results indicate that a daily dose of lycopene exerts a protective effect against EIA in some patients, most probably through an in vivo antioxidative effect.