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.

Inert gas washout tests, performed using the single-or multiple-breath washout technique, were first described over 60 years ago. As measures of ventilation distribution inhomogeneity, they offer complementary information to standard lung function tests, such as spirometry, as well as improved feasibility across wider age ranges and improved sensitivity in the detection of early lung damage. These benefits have led to a resurgence of interest in these techniques from manufacturers, clinicians and researchers, yet detailed guidelines for washout equipment specifications, test performance and analysis are lacking. This manuscript provides recommendations about these aspects, applicable to both the paediatric and adult testing environment, whilst outlining the important principles that are essential for the reader to understand. These recommendations are evidence based, where possible, but in many places represent expert opinion from a working group with a large collective experience in the techniques discussed.Finally, the important issues that remain unanswered are highlighted. By addressing these important issues and directing future research, the hope is to facilitate the incorporation of these promising tests into routine clinical practice.

This statement summarizes the information available on specific exercise test protocols and outcome parameters used in patients with cystic fibrosis (CF) and provides expert consensus recommendations for protocol and performance of exercise tests and basic interpretation of results for clinicians. The conclusions were reached employing consensus meetings and a wide-band Delphi process. Although data on utility are currently limited, standardized exercise testing provides detailed information on physiological health, allows screening for exercise-related adverse reactions and enables exercise counselling. The Godfrey Cycle Ergometer Protocol with monitoring of oxygen saturation and ventilatory gas exchange is recommended for exercise testing in people 10 years and older. Cycle ergometry only with pulse oximetry using the Godfrey protocol or treadmill exercise with pulse oximetry - preferably with measurement of gas exchange - are second best options. Peak oxygen uptake, if assessed, and maximal work rate should be reported as the primary measure of exercise capacity. The final statement was reviewed by the European Cystic Fibrosis society and revised based on the comments received. The document was endorsed by the European Respiratory Society.

Highlights d Organoids of CF patients were used to quantitate individual drug response in vitro d Organoid responses correlate with two clinical response parameters ppFEV 1 and SCC d In vivo (non)responders were identified with a PPV of 100% and a NPV of 80%

The aim of this study was to evaluate the applicability of American Thoracic Society and European Respiratory Society criteria for spirometry in children.Maximal expiratory flow/volume (MEFV) measurements from 446 school-age children, experienced in performing MEFV manoeuvres, were studied and acceptability (start-of-test (backward extrapolated volume as a percentage of forced vital capacity (FVC) (Vbe%FVC) or as an absolute value (Vbe), end-of-test (forced expiratory time (FET)) and reproducibility criteria (absolute and percentage difference between best and second-best FVC and forced expiratory volume in one second (FEV1) (DFVC, DFVC %, DFEV1 and DFEV1 %)) were applied to these manoeuvres.The Vbe%FVC criterion was met by 91.5%, the Vbe v0.15 L criterion by 94.8% and the Vbe v0.10 L by 60.1% of children. Vbe v0.15 L appeared to be a more useful parameter than Vbe%FVC. The FET criterion was met by only 15.3% of children. DFVC v0.2 L and DFEV1 v0.2 L were met by 97.1% and 98.4%, and DFVC v0.1 L and DFEV1 v0.1 L by 79.8% and 84.3% of the children, respectively. These criteria appeared to be less useful compared to percentage criteria (DFVC % and DFEV1 %). Even experienced children did not meet all international criteria for spirometry. However, most of their MEFV curves are useful for interpretation.Based on the performance of these children, a re-evaluation of criteria for maximal expiratory flow/volume measurements in children is proposed.

The impulse oscillometry system (IOS) was introduced as a new technique to assess airflow obstruction in patients who are not able to perform forced breathing maneuvers, e.g., subjects with cerebral palsy or severe mental retardation, and young children. This study evaluates the sensitivity and specificity of IOS parameters to quantify changes in airflow obstruction in comparison with forced expiratory volume in the first second (FEV(1)) and peak expiratory flow (PEF) measurements. Measurements of FEV(1), PEF, and resistance (R) and reactance (X) at frequencies of 5-35 Hz were performed in 19 children with asthma before, during, and after methacholine challenge and subsequent bronchodilatation. All parameters changed significantly during tests. Values of R5 and R10 correlated with FEV(1) (r = -0.71 and -0.73, respectively, P < 0.001), as did values of X5 and X10 (r = 0.52 and 0.57, respectively, P < 0.01). Changes in R preceded changes in PEF and FEV(1) during methacholine challenge. The area under the receiver operating characteristic (ROC) curve to predict a 15% fall in FEV(1) showed better sensitivity and specificity for R5 (area under the curve, 0.85) compared to PEF (0.79) or R10 (0.73). We conclude that IOS parameters can be easily used as an indirect measure of airflow obstruction. This might be helpful in patients who are not able to perform forced breathing maneuvers. In individual subjects, R values measured at 5 Hz showed to be superior to PEF measurements in the detection of a 15% fall in FEV(1).

These new paediatric reference equations provide accurate estimates of the range of normality for most commonly used pulmonary function indices, resulting in less underdiagnosis and overdiagnosis of pulmonary diseases.

Pulmonary function and nutritional status are important determinants of exercise capacity in patients with cystic fibrosis (CF). Studies investigating the effects of determinants, such as genotype or infection and inflammation, are scarce and have never been analysed in a multivariate longitudinal model.A prospective longitudinal cohort study was performed to evaluate whether genotype, chronic inflammation and infection were associated with changes in exercise capacity. Furthermore, we investigated whether exercise capacity can predict clinical outcome.504 exercise tests of 149 adolescents with CF were evaluated. Maximal oxygen uptake corrected for body mass % predicted declined 20% during adolescence, and was associated with immunoglobulin (Ig)G levels and chronic Pseudomonas aeruginosa infection. A lower exercise capacity was associated with a higher mortality, steeper decline in pulmonary function and greater increase in IgG levels.Since a decline in exercise capacity during adolescence was negatively associated with IgG levels and chronic P. aeruginosa infection, these data emphasise the importance of prevention and treatment of chronic inflammation and infections in patients with CF. Furthermore, a lower exercise capacity was associated with a higher mortality rate, steeper decline in pulmonary function and higher increase in IgG levels with increasing age in adolescents with CF. This stresses the value of regular exercise testing for assessing prognosis in adolescents with CF.