Time spent in vigorous physical activity is associated with increased exhaled nitric oxide in non-asthmatic adolescents.

INTRODUCTION: Physical activity (PA) is important in preventing disease, but endurance elite athletes have increased prevalence of asthma and airway inflammation. OBJECTIVES: We aimed to determine if PA was associated with increased fractional exhaled nitric oxide (FENO ) in asthmatic and non-asthmatic adolescents. METHODS: FENO was recorded (Niox Mino®, Aerocrine AB, Stockholm, Sweden) in 169 adolescents (13-14 years) in a nested case-control analysis from the Environment and Childhood Asthma study, Oslo, 92 adolescents with and 77 without asthma. They underwent clinical examination, lung function measurements and treadmill run measuring peak oxygen uptake, and objectively recorded PA for four consecutive days. PA was classified as moderate, vigorous and very vigorous, and total number of hours of each category was recorded for each subject. Associations between FENO and PA were tested using linear robust multiple regression analyses. RESULTS: In non-asthmatic adolescents, FENO was associated with daily hours of vigorous to very vigorous (r=0.27, P=0.02) and very vigorous PAs (r=0.25, P=0.036) in bivariate analyses. In multivariate analyses, FENO was associated with vigorous to very vigorous PA [regression coefficients (95% confidence interval) 1.9 (0.6, 3.1); P=0.004] and more strongly with very vigorous PA [3.9 (1.5, 6.4); P=0.002] in non-asthmatic but not in asthmatic adolescents. Total daily PA was not associated with FENO in either group. Thus, 1 h of very vigorous PA per day increased FENO by 3.9ppb. CONCLUSION: Vigorous to very vigorous PA, contrasting total daily PA, was significantly associated with increased FENO in non-asthmatic adolescents, suggesting that intensive PA may induce airway inflammation independent of asthma.

Eoxins: a new inflammatory pathway in childhood asthma.

BACKGROUND: Increased levels of leukotrienes (LTs) in exhaled breath condensate (EBC) are associated with asthma and bronchial hyperresponsiveness (BHR), whereas eicosanoids generated through the 15-lipoxygenase (LO) pathway (15-hydroxyeicosatetraenoic acid [HETE] and eoxins) have been less studied. OBJECTIVE: We investigated whether metabolites of the 5- and 15-LO pathways in EBC are associated with childhood asthma, asthma severity, and clinical parameters. METHODS: The present study included 131 school-aged children (27 children with problematic severe asthma, 80 children with mild-to-moderate asthma, and 24 healthy children) from the Severe Asthma Recognized in Childhood study and 19 children with other nonasthmatic chronic lung diseases. Clinical work-up included spirometry, fractional exhaled nitric oxide measurements, skin prick testing, and methacholine challenge. Eicosanoids were analyzed in EBC by using mass spectrometry and are reported as concentrations (in picograms per milliliter) and eicosanoid/palmitic acid (PA) ratios. RESULTS: Eoxin C4/PA, eoxin D4/PA, eoxin E4/PA, 15-HETE/PA, and LTC4/PA ratios were significantly increased in asthmatic versus healthy children. Eoxin D4/PA and LTE4/PA ratios were also significantly higher in children with BHR. A nonsignificant trend was observed toward higher eoxin/PA ratios with increasing asthma severity. In contrast to asthma, children with chronic lung disease had the highest 15-HETE/PA, LTC4/PA, LTE4/PA, and LTB4/PA ratios. CONCLUSION: The results point to increased activity of the 15-LO inflammatory pathway in childhood asthma. Mass spectrometric analyses of EBC demonstrate that increased eoxin levels not only accompany the increased 5-LO product LTC4 but are also associated with BHR. These markers might represent a new therapeutic target for asthma treatment.

Asthma severity in childhood, untangling clinical phenotypes.

Assessment of childhood asthma severity and asthma control encompasses heterogeneous clinical presentations. The relationship between patterns of asthma symptoms and objective measurements is poorly defined in paediatric asthma. This study includes 115 asthmatic schoolchildren, of which 31 were at inclusion defined as Problematic severe asthma because of inadequate asthma control in the presence of high-dose inhaled corticosteroid (HD-ICS) treatment and at least one other asthma controller drug. Two partially overlapping clinical outcomes were defined irrespective of severity classification (Exacerbations and Chronic persistent asthma) in patients with uncontrolled asthma. The same symptom criteria were used as for Problematic severe asthma, but disregarding current medication. Lung function, exhaled nitric oxide (FE(NO)), bronchial hyperresponsiveness, allergic sensitization and Quality of life (QoL) in the symptom subgroups were compared to children with well-controlled asthma. Multifactor analysis was performed to assess the relative explanatory power of clinical asthma presentations and of HD-ICS treatment on objective measurements. Whereas children included in the Exacerbations subgroup had objective features similar to patients with well-controlled asthma, the Chronic persistent asthma subgroup demonstrated significantly reduced lung function, increased immunoglobin E, allergic poly-sensitization and impaired QoL, similar to that in patients pre-defined as Problematic severe asthma. The presence of chronic asthma symptoms was a significant explanatory factor for reduced lung function, QoL and increased FE(NO) in multifactor analysis. Differences in objective measurements suggest that children with Chronic persistent asthma and those who are symptomatic predominantly during exacerbations may represent distinct phenotypes of childhood asthma with different clinical prognoses.