8-Isoprostane in exhaled breath condensate and exercise-induced bronchoconstriction in asthmatic children and adolescents.

BACKGROUND Exercise-induced bronchoconstriction (EIB) in the asthmatic child is associated with persistent airway inflammation and poor disease control. EIB could arise partly from airway oxidative stress. Exhaled breath condensate (EBC) levels of 8-isoprostane (IsoP), which is a known marker of oxidative stress, might therefore be helpful for monitoring asthma noninvasively. METHODS We recruited 46 asthmatic children and adolescents 6 to 17 years of age (29 boys), all of whom underwent lung function testing, measurement of the fractional concentration of exhaled nitric oxide (FENO), and collection of EBCs for 8-IsoP measurement before and after exercise challenge. FENO was measured before exercise and 5 min and 20 min after exercise. Spirometry was repeated 1, 5, 10, 15, and 20 min after exercise. RESULTS Baseline 8-IsoP levels (but not baseline FENO levels) correlated with the fall in FEV(1) 5 min after exercise (r = - 0.47; p = 0.002). 8-IsoP levels measured after exercise remained unchanged from baseline levels; conversely, FENO levels decreased in parallel with the decline in FEV(1) at 5 min (r = 0.44; p = 0.002). The mean baseline 8-IsoP concentrations were higher in patients with EIB (n = 12) than in those without EIB (n = 34; 44.9 pg/mL [95% confidence interval (CI), 38.3 to 51.5] vs 32.3 pg/mL [95% CI, 27.6 to 37.0], respectively; p < 0.01). No difference was found in the mean baseline FENO between groups (with EIB group: 38.7 ppb; 95% CI, 24.5 to 61.1; without EIB group: 29.1 ppb; 95% CI, 22.0 to 38.4). CONCLUSIONS Increased 8-IsoP concentrations in EBC samples of asthmatic children and adolescents with EIB suggest a role for oxidative stress in bronchial hyperreactivity.

[1]  P. Montuschi,et al.  Isoprostanes: markers and mediators of oxidative stress , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[2]  I. Horváth,et al.  Combined use of exhaled hydrogen peroxide and nitric oxide in monitoring asthma. , 1998, American journal of respiratory and critical care medicine.

[3]  John L. Hankinson,et al.  Standardization of Spirometry, 1994 Update. American Thoracic Society. , 1995, American journal of respiratory and critical care medicine.

[4]  H. Bisgaard,et al.  Exhaled nitric oxide predicts exercise-induced bronchoconstriction in asthmatic school children. , 2005, Chest.

[5]  E. Baraldi,et al.  Exhaled nitric oxide and exercise-induced bronchoconstriction in asthmatic children. , 2000, American journal of respiratory and critical care medicine.

[6]  P. J. Barnes,et al.  Exhaled breath condensate: methodological recommendations and unresolved questions , 2005, European Respiratory Journal.

[7]  L. Niskanen,et al.  Blood glutathione homeostasis as a determinant of resting and exercise-induced oxidative stress in young men. , 1999, Redox report : communications in free radical research.

[8]  S. Anderson,et al.  An exercise challenge for epidemiological studies of childhood asthma: validity and repeatability. , 1995, The European respiratory journal.

[9]  M. Corradi,et al.  Aldehydes and glutathione in exhaled breath condensate of children with asthma exacerbation. , 2003, American journal of respiratory and critical care medicine.

[10]  B. Fulkerson,et al.  Generation of reactive oxygen species after exhaustive aerobic and isometric exercise. , 2000, Medicine and science in sports and exercise.

[11]  P. Montuschi,et al.  Increased exhaled 8-isoprostane in childhood asthma. , 2003, Chest.

[12]  P. Montuschi,et al.  Increased nitrosothiols in exhaled breath condensate in inflammatory airway diseases. , 2001, American journal of respiratory and critical care medicine.

[13]  M. Martins,et al.  Exercise-induced bronchospasm in children: effects of asthma severity. , 1999, American journal of respiratory and critical care medicine.

[14]  P. Montuschi,et al.  Increased 8-isoprostane, a marker of oxidative stress, in exhaled condensate of asthma patients. , 1999, American journal of respiratory and critical care medicine.

[15]  T. Barstow,et al.  The effect of exercise intensity on lipid peroxidation. , 1997, Medicine and science in sports and exercise.

[16]  M. Delaire,et al.  Bronchial obstruction and exhaled nitric oxide response during exercise in cold air. , 1998, The European respiratory journal.

[17]  K. Carlsen,et al.  Low‐dose budesonide improves exercise‐induced bronchospasm in schoolchildren , 2000, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[18]  Arthur S Slutsky,et al.  Marked flow-dependence of exhaled nitric oxide using a new technique to exclude nasal nitric oxide. , 1997, American journal of respiratory and critical care medicine.

[19]  T. Art,et al.  Effect of exercise and COPD crisis on isoprostane concentration in plasma and bronchoalveolar lavage fluid in horses. , 2010, Equine veterinary journal. Supplement.

[20]  T. Kaminski,et al.  Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise. , 2001, Free radical biology & medicine.

[21]  D. Amundson,et al.  Exhaled nitric oxide as a predictor of exercise-induced bronchoconstriction. , 2003, Chest.

[22]  K. Hinchcliff,et al.  Oxidant stress in sled dogs subjected to repetitive endurance exercise. , 2000, American journal of veterinary research.

[23]  H. Levison,et al.  The response to exercise in normal and asthmatic children. , 1978, The Journal of pediatrics.

[24]  M. Barreto,et al.  Reduced Exhaled Nitric Oxide in Children After Testing of Maximal Expiratory Pressures , 2006, Pediatric pulmonology.

[25]  P. Gibson,et al.  Noninvasive assessment of airway inflammation in children: induced sputum, exhaled nitric oxide, and breath condensate. , 2000, The European respiratory journal.

[26]  Eleri Jones,et al.  Electron spin resonance spectroscopic detection of oxygen-centred radicals in human serum following exhaustive exercise , 1998, European Journal of Applied Physiology and Occupational Physiology.

[27]  R. Pauwels,et al.  GLOBAL STRATEGY FOR ASTHMA MANAGEMENT AND PREVENTION , 1996 .

[28]  S. Nakaji,et al.  Capacity of circulating neutrophils to produce reactive oxygen species after exhaustive exercise. , 1996, Journal of applied physiology.

[29]  P. Barnes,et al.  Increased nitrotyrosine in exhaled breath condensate of patients with asthma. , 2000, American journal of respiratory and critical care medicine.

[30]  S. Anderson,et al.  Monitoring asthma therapy using indirect bronchial provocation tests * , 2007, The clinical respiratory journal.

[31]  M. Barreto,et al.  Off‐line exhaled nitric oxide measurements in children , 2001, Pediatric pulmonology.

[32]  Paolo Montuschi,et al.  Analysis of exhaled breath condensate for monitoring airway inflammation. , 2002, Trends in pharmacological sciences.

[33]  M. Barreto,et al.  Additive effect of eosinophilia and atopy on exhaled nitric oxide levels in children with or without a history of respiratory symptoms , 2005, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[34]  J. Morrow,et al.  Antioxidant supplementation prevents exercise-induced lipid peroxidation, but not inflammation, in ultramarathon runners. , 2004, Free radical biology & medicine.

[35]  G. Polgar,et al.  Pulmonary Function Testing in Children: Techniques and Standards , 1977 .

[36]  J. Morrow,et al.  Prolonged exercise, lymphocyte apoptosis and F2-isoprostanes , 2002, European Journal of Applied Physiology.

[37]  K. Kostikas,et al.  Exhaled breath condensate in patients with asthma: implications for application in clinical practice , 2008, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[38]  P. Barnes,et al.  Exhaled biomarkers. , 2006, Chest.

[39]  H. Togari,et al.  Exhaled nitric oxide decreases during exercise-induced bronchoconstriction in children with asthma. , 2001, American journal of respiratory and critical care medicine.

[40]  J. Hankinson,et al.  Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. , 2000, American journal of respiratory and critical care medicine.

[41]  P. Montuschi,et al.  Validation of 8-isoprostane and prostaglandin E2 measurements in exhaled breath condensate , 2003, Inflammation Research.

[42]  M. Corradi,et al.  Exhaled breath condensate cysteinyl leukotrienes are increased in children with exercise-induced bronchoconstriction. , 2005, The Journal of allergy and clinical immunology.

[43]  The isoprostanes: Unique bioactive products of lipid peroxidation , 1997 .

[44]  A. Custovic,et al.  Exhaled nitric oxide, sensitization, and exposure to allergens in patients with asthma who are not taking inhaled steroids. , 1999, American journal of respiratory and critical care medicine.

[45]  P. Barnes,et al.  Exhaled 8-isoprostane in childhood asthma , 2005, Respiratory research.