on behalf of the American Thoracic Society/ European Respiratory Society Working Group on Infant and Young Children Pulmonary Function Testing This official statement of the American Thoracic Society (ATS) and the European Respiratory Society (ERS) was approved by the ATS Board of Directors, September 2006, and the ERS Executive Committee, December 2006 6. Further multidisciplinary work is required to investigate the best combination of tests (e.g., structure, function, inflammation, atopy) and challenges (e.g., pharmaceutical vs. physical) to investigate specific clinical entities during early childhood.

There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis.Based on the limited evidence available, inhaled short-acting b 2 -agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop.Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit.Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

Exhaled nitric oxide (FE(NO)) has been proposed as a noninvasive marker of airway inflammation in asthma, and may reflect airway eosinophilia. We examined the relationship between FE(NO) and eosinophilic inflammation in endobronchial biopsies from 31 children with difficult asthma (mean age [range] 11.9 [6-17] yr), following 2 wk of prednisolone (40 mg/d). Endobronchial biopsy was also performed in seven children without asthma. Biopsy eosinophils were detected using antibody to major basic protein, and point-counting used to derive an "eosinophil score." FE(NO) readings and suitable biopsies for analysis were both obtained in 21 of 31 children with asthma. Adherence to prednisolone was demonstrated in 17 of these 21. Within this group, there was a correlation between FE(NO) and eosinophil score (r = 0.54, p = 0.03). The relationship was strongest in patients with persistent symptoms after prednisolone, in whom FE(NO) > 7 ppb was associated with a raised eosinophil score. For all patients, FE(NO) < 7 ppb was associated with an eosinophil score within the nonasthmatic range, regardless of symptoms. We propose that FE(NO) is associated with eosinophilic inflammation in children with difficult asthma, following prednisolone, and may help in identifying patients in whom persistent symptoms are associated with airway eosinophilia.

The use of noninvasive methods of monitoring airway inflammation, such as exhaled nitric oxide (eNO) and induced sputum, has been shown to improve asthma monitoring and optimize treatment in adult patients with asthma. There is a lack of comparable data in children. Forty children with stable asthma eligible for inhaled steroid reduction were reviewed every 8 weeks, and their inhaled steroid dose halved if clinically indicated. eNO, sputum induction combined with bronchial hyperreactivity testing, and exhaled breath condensate collection were performed at each visit to predict success or failure of reduction of inhaled steroids. Thirty of 40 (75%) children tolerated at least one dose reduction, 12 of 40 (30%) were successfully weaned off, and in total, 15 of 40 (38%) children experienced loss of asthma control. Treatment reduction was successful in all children who had no eosinophils in induced sputum before the attempted reduction. Using multiple logistic regression, increased eNO (odds ratio, 6.3; confidence interval, 3.75-10.58) and percentage of sputum eosinophils (odds ratio, 1.38; confidence interval, 1.06-1.81) were significant predictors of failed reduction. These findings suggest that monitoring airway inflammation may be useful in optimizing treatment in children with asthma.

Nurse-led assessments including a home visit can help identify potentially modifiable factors for poorly controlled symptoms in children with problematic asthma.

Background: The levels of exhaled and nasal nitric oxide (eNO and nNO) in groups of patients with inflammatory lung diseases are well documented but the diagnostic use of these measurements in an individual is unknown. Methods: The levels of nNO and eNO were compared in 31 children with primary ciliary dyskinesia (PCD), 21 with non-CF bronchiectasis (Bx), 17 with cystic fibrosis (CF), 35 with asthma (A), and 53 healthy controls (C) using a chemiluminescence NO analyser. A diagnostic receiver-operator characteristic (ROC) curve for PCD using NO was constructed. Results: The median (range) levels of nNO in parts per billion (ppb) in PCD, Bx, CF, and C were 60.3 (3.3-920), 533.6 (80-2053), 491.3 (31-1140), and 716 (398-1437), respectively; nNO levels were significantly lower in PCD than in all other groups (p<0.05). The median (range) levels of eNO in ppb in PCD, Bx, CF, A, and C were 2.0 (0.2-5.2), 5.4 (1.0-22.1), 2.6 (0.8-12.9), 10.7 (1.6-46.7), and 4.85 (2.5-18.3), respectively. The difference in eNO levels in PCD reached significance (p<0.05) when compared with those in Bx, A and C but not when compared with CF. Using the ROC curve, nNO of 250 ppb showed a sensitivity of 97% and a specificity of 90% for the diagnosis of PCD. Conclusions: eNO and nNO cannot be used diagnostically to distinguish between most respiratory diseases. However, nNO in particular is a quick and useful diagnostic marker which may be used to screen patients with a clinical suspicion of PCD.

Cysteinyl leukotrienes (cys-LTs; LTC4, LTD4, and LTE4) are generated predominantly by mast cells and eosinophils and induce airway smooth muscle contraction, microvascular leakage, and mucous hypersecretion whereas leukotriene B4 (LTB4) is a potent chemoattractant of neutrophils. We measured cys-LTs and LTB4 in exhaled breath condensate from children aged 7-14 years including healthy nonatopic children (n = 11) and children with mild intermittent asthma (steroid naive, n = 11), mild persistent asthma (low-dose inhaled steroid treatment, n = 13), or moderate to severe persistent asthma (high-dose inhaled steroid treatment, n = 13). Exhaled LTB4 levels were increased in patients with mild and moderate to severe persistent asthma compared with patients with mild intermittent asthma (126.0 +/- 8.8 and 131.9 +/- 7.1 versus 52.7 +/- 3.8 pg/ml, p < 0.001 and p < 0.0001) and normal subjects (126.0 +/- 8.8 and 131.9 +/- 7.1 versus 47.9 +/- 4.1 pg/ml, p < 0.0001). Elevated exhaled cys-LT levels were found in patients with mild and moderate to severe persistent asthma compared with normal subjects (27.9 +/- 2.8 and 31.5 +/- 4.5 versus 18.5 +/- 0.5 pg/ml, p < 0.01 and p < 0.05). There was an inverse correlation between exhaled cys-LTs and LTB4 in patients with mild persistent asthma. We conclude that exhaled cys-LTs and LTB4 may be noninvasive markers of airway inflammation in pediatric asthma.

Background Two distinct, stable inflammatory phenotypes have been described in adults with asthma: eosinophilic and non-eosinophilic. Treatment strategies based on these phenotypes have been successful. This study evaluated sputum cytology in children with asthma to classify sputum inflammatory phenotypes and to assess their stability over time. Methods Sputum induction was performed in 51 children with severe asthma and 28 with mild to moderate asthma. Samples were classified as eosinophilic (>2.5% eosinophils), neutrophilic (>54% neutrophils); mixed granulocytic (>2.5% eosinophils, >54% neutrophils); or paucigranulocytic (#2.5% eosinophils, #54% neutrophils). Sputum induction was repeated every 3 months in children with severe asthma (n¼42) over a 1-year period and twice in mild to moderate asthma (n¼17) over 3e6 months.Results 62 children (78%) had raised levels of inflammatory cells in at least one sputum sample. In the longitudinal analysis 37 of 59 children (63%) demonstrated two or more phenotypes. Variability in sputum inflammatory phenotype was observed in both the severe and the mild to moderate asthma groups. Change in phenotype was not related to change in inhaled corticosteroid (ICS) dose or asthma control, nor was it reflected in a change in exhaled nitric oxide (FE NO ). 24 children (41%) fulfilled the criteria for noneosinophilic asthma on one occasion and eosinophilic on another. There were no differences in severity, asthma control, atopy, ICS dose or forced expiratory volume in 1 s between those who were always non-eosinophilic and those always eosinophilic. Conclusion Raised levels of inflammatory cells were frequently found in children with asthma of all severities. Sputum inflammatory phenotype was not stable in children with asthma.