This is the first report indicating that cardiopulmonary fitness is equally and consistently reduced in both children with PCD and CF along with a consistent lower pulmonary function in PCD compared with CF. A certain reservation for possible selection bias and the small number of patients is necessary. However, increased focus on early diagnosis, evidence-based treatment regimens and close clinical monitoring in PCD are warranted.

The use of pulmonary function tests (PFTs) has been widely described in airway diseases like asthma and cystic fibrosis, but for children's interstitial lung disease (chILD), which encompasses a broad spectrum of pathologies, the usefulness of PFTs is still undetermined, despite widespread use in adult interstitial lung disease. A literature review was initiated by the COST/Enter chILD working group aiming to describe published studies, to identify gaps in knowledge and to propose future research goals in regard to spirometry, whole-body plethysmography, infant and pre-school PFTs, measurement of diffusing capacity, multiple breath washout and cardiopulmonary exercise tests in chILD. The search revealed a limited number of papers published in the past three decades, of which the majority were descriptive and did not report pulmonary function as the main outcome.PFTs may be useful in different stages of management of children with suspected or confirmed chILD, but the chILD spectrum is diverse and includes a heterogeneous patient group in all ages. Research studies in well-defined patient cohorts are needed to establish which PFT and outcomes are most relevant for diagnosis, evaluation of disease severity and course, and monitoring individual conditions both for improvement in clinical care and as end-points in future randomised controlled trials.

To date, human umbilical cord blood (CB) has been employed successfully in well over 1000 allogeneic (unrelated and sibling) stem cell transplantations. Because of primary limitations in volume and cell numbers, over 90% of these transplantations were performed in children. Therefore requests for well standardised cord blood units of high quality are now increasing constantly. Examination and standardisation of unrelated and related cord blood stem cell preparations and banking as well as their biological characterisation was already initiated in Düsseldorf in 1992. Hitherto a total of 3236 CB samples with a mean volume of 89 +/- 25 ml, a mean total number of nucleated cells (NC) of 10 +/- 5 x 10(8) and a mean number of CFU-GM of 6 +/- 5 x 10(5) have also been validated by haematological, immunological and microbiological criteria. In addition to that, 97 directed CB donations of siblings with a clinical indication have been characterised and banked along the same lines. All CB units were collected from the umbilical cord vein immediately after vaginal full term delivery or caesarean section, then frozen and stored in liquid nitrogen. 1940 CB units were stored unseparated, the other 1296 were volume reduced using Hetastarch (HES) with a mean recovery of 85 +/- 13% of the nucleated cells, 86 +/- 12% and 84 +/- 13% for CFC and CD34+ cells, respectively. Only 5.0 ml of a CB sample is required for routine laboratory testing as there are HLA-class I typing, HLA-class II typing by sequence specific oligonucleotide probes (PCR-SOP), ABO typing, sterility control, assessment of progenitor and stem cells by colony forming assays, and CD34+ status as well as certain viral infections such as CMV, Hepatitis B, C, HIV, Parvo B19 by PCR technology before releasing the CB unit for transplantation. For apparent viral infections, maternal sera obtained at birth were tested for HBsAg, anti-HBc, anti-HCV, -HAV-(IgG, IgM), -HIV-1-2, -EBV- (IgG, IgM), -HTLVI-II, -CMV (IgM, IgG), toxoplasmosis and syphilis. Within the last three years a total of 4860 preliminary searches and 680 extended unit reports were submitted to the CB bank Düsseldorf by fax or World Wide Web. So far 68 unrelated and 3 related CB units were delivered. From these 70 have been transplanted in 30 different transplant centres world-wide. Until now the evaluation of the first 53 unrelated CB-transplantations was performed together with the EUROCORD transplant registry. Three patients were excluded from the analysis, since they received an unrelated CB-transplant for non-engraftment after previous allotransplants. The median patient age of these 50 patients was 5.0 years (range 0.3-44), the median weight 18 kg (range 4-70 kg). The majority of the patients transplanted for malignancies (66%) suffered from ALL (n = 19), AML (n = 7), CML (n = 4) and lymphoma (n = 2) with two third (75%) in an intermediate (2nd CR) or advanced stage of disease (> 2nd CR); 13 patients had metabolic diseases and immunodeficiencies and three had aplastic anaemia. All CB samples as well as th...

Background and objective: Cross-sectional and longer-term studies have demonstrated abnormal yet stable multiple-breath inert gas washout (MBW) indices in patients with primary ciliary dyskinesia (PCD). This study aimed to assess the intermediate term evolution and the betweenoccasion variability of MBW indices in PCD over 1 year. Methods: Children and young adults with a confirmed diagnosis of PCD were included in this single-centre, prospective, observational, longitudinal study. Over 1 year, nitrogen (N 2) MBW and spirometry were performed at three occasions during ordinary scheduled outpatient visits. Trends and variability in lung clearance index (LCI), moment ratios, normalized N 2 concentration at six lung volume turnovers, and regional ventilation inhomogeneity indices of the conducting and intra-acinar airways (S cond *V T and S acin *V T) were analysed using linear mixed models. Results: Forty-two patients, aged 6-29 years (median: 15.4), performed 116 N 2 MBW test occasions and 96.6% were technically acceptable. A minimal, although significant, increase in LCI over 1 year (mean: 0.51 units, 95% CI: 0.12-0.91, p = 0.01) was found; while, all other N 2 MBW indices and FEV 1 remained unchanged. A moderate correlation was observed between LCI and FEV 1 (r = −0.47, p = 0.0001). The limits of agreement between tests 1 year apart were for LCI: −1.96 to 2.98; S cond *V T : ± 0.039; S acin *V T : −0.108 to 0.128. Conclusions: Children and young adults with PCD managed at a specialist centre showed slightly, but significant, increasing LCI and otherwise unchanged ventilation inhomogeneity indices and dynamic volumes over the intermediate term of 1 year. Estimates of the variability of N 2 MBW indices may inform sample size calculations of future randomized controlled trials.

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Background: Severe postinfectious diffuse pulmonary disease may clinically mimic other entities of children's interstitial lung disease and is clinically challenging comprising various disease severities despite treatment. Long-term lung function trend and physical capacity in children with postinfectious diffuse pulmonary disease are rarely reported. We investigated trends in pulmonary function by long-term follow-up and assessed physical capacity in such patients. Methods: We performed a descriptive, single-center follow-up study in children with biopsy-verified postinfectious diffuse pulmonary disease. Patients with completed primary treatment course were eligible for follow-up, including pulmonary function and exercise (VO 2peak ) testing. Results: Thirty patients with postinfectious diffuse pulmonary disease were identified and included. Median (range) age at diagnose was 27.5 (2–172) months after a mean lag time of 23 months. H. influenzae and rhinovirus were the most frequent pathogens. Fifteen patients were available for follow-up after mean (range) 7.6 (2–15) years of treatment completion. Lung clearance index (LCI 2.5 ), forced expiratory volume in 1 second (FEV 1 ), and bronchodilator responsiveness were abnormal in 80%, 53%, and 44%, respectively. Diffusion capacity for monoxide was abnormal in 7% and total lung capacity in 33%. Only 8% demonstrated low VO 2peak , while 40% reported difficulties during physical exertion. Longitudinal data on spirometry ( n = 14) remained unchanged from end of treatment throughout follow-up. A significant association was found between zLCI 2.5 and zFEV 1 (multiple linear regression; r 2 = 0.61; P = 0.0003). Conclusion: Postinfectious diffuse pulmonary disease in children carries a varying degree of chronic pulmonary impairment with onset of symptoms in the first months of life and a typical considerable lag time before diagnosis. Follow-up several years after the initial injury demonstrated moderate-to-severe peripheral airway impairment although no further lung function decline was found years after completion of treatment. Despite acceptable VO 2peak , a considerable proportion struggled during heavy exercise.

Isomerism, also known as heterotaxy, is a clinical entity that impacts multiple organ systems both anatomically and functionally. The airways and lungs are involved in a great number of these patients, leading to increased sinopulmonary symptoms, increased need for oxygenation, and increased postoperative ventilatory support. Additionally, these patients often have congenital heart disease requiring Fontan palliation. What has not been previously described, and is the focus of this study, is the results of cardiopulmonary exercise testing in those who have undergone Fontan palliation with and without isomerism. We have now compared these finding with those from patients with primary ciliary dyskinesia, as many patients with isomerism have ciliary dyskinesia. We identified patients having the Fontan circulation with and without isomerism who had undergone cardiopulmonary exercise testing, comparing the findings from healthy individuals undergoing exercise, and a comparable number of individuals with primary ciliary dyskinesia but no congenital heart disease. We were able to include a total of 68 patients in our study, with 17 in each of the four groups. Cardiopulmonary exercise testing yielded the best results in healthy patients. All patients with the Fontan circulation demonstrated mixed pulmonary disease, although those with isomerism had greater FVC and FEV1. Exercise times did not differ, although peak consumption of oxygen was greater in those with isomerism. Those with ciliary dyskinesia had only obstructive pulmonary disease and had the lowest FEF25-75 between all groups. Those with isomerism had a lesser degree of obstructive pulmonary disease when compared to those with primary ciliary dyskinesia. Patients with the Fontan circulation with and without isomerism have relatively subtle differences in their cardiopulmonary exercise testing, with both groups demonstrating restrictive lung disease. In regard to obstructive lung disease, those with isomerism tend to be more similar to the patients with primary ciliary dyskinesia than those with the Fontan circulation but without isomerism. The results are likely limited by selection bias and highlight the need for multicentric efforts to characterize cardiopulmonary exercise testing in those patients with pulmonary isomerism.