Background: Exhaled nitric oxide has been proposed as a marker for airway inflammation in asthma. The aim of this study was to compare exhaled nitric oxide levels with inflammatory cells and mediators in bronchoalveolar lavage fluid from asthmatic and normal children. Methods: Children were recruited from elective surgical lists and a non-bronchoscopic bronchoalveolar lavage (BAL) was performed after induction of anaesthesia. Exhaled nitric oxide (parts per billion) was measured by two techniques: tidal breathing and restricted breath. Results: Median (interquartile range) exhaled nitric oxide measured by restricted breath was increased in asthmatics compared with normal children (24.3 (10.5-66.5) v 9.7 (6.5-16.5), difference between medians 14.6 (95% CI 5.1 to 29.9), p=0.001). In asthmatic children exhaled nitric oxide correlated significantly with percentage eosinophils (r=0.78, p<0.001 (tidal breathing) and r=0.78, p<0.001 (restricted breath)) and with eosinophilic cationic protein (r=0.53, p<0.01 (restricted breath)), but not with other inflammatory cells in the BAL fluid. The area under the receiver operator characteristic curves for the prediction of the presence of eosinophilic airways inflammation by exhaled nitric oxide (tidal and restricted) was 0.80 and 0.87, respectively. Conclusions: Exhaled nitric oxide correlates closely with percentage eosinophils in BAL fluid in asthmatic children and is therefore likely to be a useful non-invasive marker of airway inflammation.

Although some asthmatic children seem to recover from their asthma, 30-80% develop asthma again in later life. The underlying risk factors are unknown. The hypothesis for this study was that children with apparently outgrown asthma would have underlying airway inflammation.Nonbronchoscopic bronchoalveolar lavage was performed on normal children (n=35) and children who had wheezed previously (n=35).Eosinophils were raised in the lavage fluid of atopic children who had apparently outgrown asthma (median (interquartile range) 0.36 (0.05-0.74) compared to controls 0.10 (0-0.18), p=0.002). There was no relationship between length of remission and degree of airways eosinophilia.Thus, there is persistent airways inflammation in some children with outgrown asthma and this may be a risk factor for future relapse.

Isolated chronic cough in childhood is a common complaint. Although the symptom cough is included in the definition of childhood asthma, there is debate as to whether the majority of these children have asthma. The authors studied children with isolated chronic cough looking for evidence of airway inflammation typical of asthma, with increased numbers of airway eosinophils as assessed from bronchoalveolar lavage (BAL).The investigations were carried out on 23 children (median age: 6.7 yrs; (range: 1.7±12.75 yrs), attending the Royal Belfast Hospital for Sick Children for elective surgery, who also had a chronic unexplained cough. Written informed consent was obtained from the parent(s) and a nonbronchoscopic BAL was performed. BAL samples were analysed for total and differential white cell counts and also for the inflammatory mediators, eosinophil cationic protein (ECP) and histamine. Results were compared with a group of normal nonatopic children and also a group of atopic asthmatic children, who had been recruited for other studies on airway inflammation.There was a small but statistically significant increase in BAL percentage eosinophils in the children with chronic cough compared with nonasthmatic controls (0.28% versus 0.10%, p=0.03). However, the children with cough had lower percentage eosinophils than the atopic asthmatic controls (0.28% versus 0.66%, p=0.01). Three out of 23 children with chronic cough had BAL eosinophils greater than the normal upper 95% reference interval in BAL. There was a small but statistically significant increase in percentage neutrophils in the children with cough compared with the nonasthmatic controls (5.85% versus 3.21%, p=0.03). Four out of the 23 children had BAL neutrophils greater than the normal upper 95% reference interval in BAL.The authors conclude that only a minority of children with chronic unexplained cough have asthmatic-type airway inflammation. It is speculated that the increased percentage neutrophils in bronchoalveolar lavage from children with cough could relate to underlying persistent airways infection.

Earlier studies in adults have indicated that increased oxidative stress may occur in the blood and airways of asthmatic subjects. Therefore the aim of this study was to compare the concentrations of antioxidants and protein carbonyls in bronchoalveolar lavage fluid of clinically stable atopic asthmatic children (AA, n ϭ 78) with our recently published reference intervals for nonasthmatic children (C, n ϭ 124). Additionally, lipid peroxidation products (malondialdehyde) in bronchoalveolar lavage fluid and several antioxidants in plasma were deter- The epithelial lining fluid of the lung with its high concentration of antioxidants provides a first line of defense against inhaled, but also endogenously produced, oxidants (1, 2). Epidemiologic studies have found an inverse association between ascorbate intake and bronchial hyperresponsivness (3). In a small group of patients with exercise-induced asthma, Cohen et al. (4) showed that supplementation with ascorbate improved lung function. Dietary supplementation with a vitamin combination (ascorbic acid, ␣-tocopherol, and ␣-carotene) also had some positive effect on lung function during exercise in combination with ozone exposure (5). Studies in adults living in the United Kingdom have shown that low intake of fresh fruit and vegetables is a risk factor for decreased lung function (6, 7). Changes in ascorbate and urate in the lining fluid of the respiratory tract have been observed as a response to acute air pollution exposure (8) and recently in adults with mild asthma (9). Inflammatory cells from peripheral blood and BAL fluid of asthmatic subjects produce more superoxide anion radicals than those of control subjects (10 -12). Treatment with corticosteroids has been shown to reduce the amount of oxygen radicals released by these cells (13).In children, asthma is defined by symptoms such as wheeze or cough (14), and we have recently shown that atopic asthma is a chronic inflammatory disease in children as in adults (15). Ongoing inflammation in the airways of children with atopic asthma may lead to enhanced oxidative stress in the epithelial lining fluid, which may, as a consequence, lead to a higher consumption of the antioxidants found in BAL fluid. Oxidative damage to BAL proteins may reflect overall oxidative stress to the respiratory tract that could contribute to the underlying pathophysiology of established asthma. We have recently reported concentrations of total ascorbate, urate, ␣-tocopherol, and oxidized proteins in BAL fluid in nonasthmatic children (16

Serum ECP and blood eosinophil percentages are useful markers for predicting eosinophilic airways inflammation in wheezing children.