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Abstract Background The clinical course of Cystic Fibrosis (CF) is usually measured using the percent predicted FEV1 and BMI Z-score referenced against a healthy population, since achieving normality is the ultimate goal of CF care. Referencing against age and sex matched CF peers may provide valuable information for patients and for comparison between CF centers or populations. Here, we used a large database of European CF patients to compute CF specific reference equations for FEV1 and BMI, derived CF-specific percentile charts and compared these European data to their nearest international equivalents. Methods 34859 FEV1 and 40947 BMI observations were used to compute European CF specific percentiles. Quantile regression was applied to raw measurements as a function of sex, age and height. Results were compared with the North American equivalent for FEV1 and with the WHO 2007 normative values for BMI. Results FEV1 and BMI percentiles illustrated the large variability between CF patients receiving the best current care. The European CF specific percentiles for FEV1 were significantly different from those in the USA from an earlier era, with higher lung function in Europe. The CF specific percentiles for BMI declined relative to the WHO standard in older children. Lung function and BMI were similar in the two largest contributing European Countries (France and Germany). Conclusion The CF specific percentile approach applied to FEV1 and BMI allows referencing patients with respect to their peers. These data allow peer to peer and population comparisons in CF patients.

Abstract Background Interstitial lung diseases (ILDs) in children represent a heterogeneous group of rare respiratory disorders that affect the lung parenchyma. After the launch of the French Reference Centre for Rare Lung Diseases (RespiRare®), we created a national network and a web-linked database to collect data on pediatric ILD. Methods Since 2008, the database has been set up in all RespiRare® centres. After patient's parents' oral consent is obtained, physicians enter the data of children with ILD: identity, social data and environmental data; specific aetiological diagnosis of the ILD if known, genetics, patient visits to the centre, and all medical examinations and tests done for the diagnosis and/or during follow up. Each participating centre has a free access to his own patients' data only, and cross-centre studies require mutual agreement. Physicians may use the system as a daily aid for patient care through a web-linked medical file, backed on this database. Results Data was collected for 205 cases of ILD. The M/F sex ratio was 0.9. Median age at diagnosis was 1.5 years old [0–16.9]. A specific aetiology was identified in 149 (72.7%) patients while 56 (27.3%) cases remain undiagnosed. Surfactant deficiencies and alveolar proteinosis, haemosiderosis, and sarcoidosis represent almost half of the diagnoses. Median length of follow-up is 2.9 years [0–17.2]. Conclusions We introduce here the French network and the largest national database in pediatric ILDs. The diagnosis spectrum and the estimated incidence are consistent with other European databases. An important challenge will be to reduce the proportion of unclassified ILDs by a standardized diagnosis work-up. This database is a great opportunity to improve patient care and disease pathogenesis knowledge. A European network including physicians and European foundations is now emerging with the initial aim of devising a simplified European database/register as a first step to larger European studies.

Abstract Interstitial lung disease (ILD) in infants and children comprises a large spectrum of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality. These disorders are characterized by inflammatory and fibrotic changes that affect alveolar walls. Typical features of ILD include dyspnea, diffuse infiltrates on chest radiographs, and abnormal pulmonary function tests with restrictive ventilatory defect and/or impaired gas exchange. Many pathological situations can impair gas exchange and, therefore, may contribute to progressive lung damage and ILD. Consequently, diagnosis approach needs to be structured with a clinical evaluation requiring a careful history paying attention to exposures and systemic diseases. Several classifications for ILD have been proposed but none is entirely satisfactory especially in children. The present article reviews current concepts of pathophysiological mechanisms, etiology and diagnostic approaches, as well as therapeutic strategies. The following diagnostic grouping is used to discuss the various causes of pediatric ILD: 1) exposure-related ILD; 2) systemic disease-associated ILD; 3) alveolar structure disorder-associated ILD; and 4) ILD specific to infancy. Therapeutic options include mainly anti-inflammatory, immunosuppressive, and/or anti-fibrotic drugs. The outcome is highly variable with a mortality rate around 15%. An overall favorable response to corticosteroid therapy is observed in around 50% of cases, often associated with sequelae such as limited exercise tolerance or the need for long-term oxygen therapy.

Abstract Background The variability in the inflammatory burden of the lung in cystic fibrosis (CF) patients together with the variable effect of glucocorticoid treatment led us to hypothesize that glucocorticoid receptor (GR) gene polymorphisms may affect glucocorticoid sensitivity in CF and, consequently, may contribute to variations in the inflammatory response. Methods We evaluated the association between four GR gene polymorphisms, TthIII, ER22/23EK, N363S and BclI, and disease progression in a cohort of 255 young patients with CF. Genotypes were tested for association with changes in lung function tests, infection with Pseudomonas aeruginosa and nutritional status by multivariable analysis. Results A significant non-corrected for multiple tests association was found between BclI genotypes and decline in lung function measured as the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC). Deterioration in FEV1 and FVC was more pronounced in patients with the BclI GG genotype compared to the group of patients with BclI CG and CC genotypes (p = 0.02 and p = 0.04 respectively for the entire cohort and p = 0.01 and p = 0.02 respectively for F508del homozygous patients). Conclusion The BclI polymorphism may modulate the inflammatory burden in the CF lung and in this way influence progression of lung function.

Abstract Background Cellular responses to aging and oxidative stress are regulated by type 1 insulin-like growth factor receptor (IGF-1R). Oxidant injury, which is implicated in the pathophysiology of a number of respiratory diseases, acutely upregulates IGF-1R expression in the lung. This led us to suspect that reduction of IGF-1R levels in lung tissue could prevent deleterious effects of oxygen exposure. Methods Since IGF-1R null mutant mice die at birth from respiratory failure, we generated compound heterozygous mice harboring a hypomorphic (Igf-1rneo) and a knockout (Igf-1r-) receptor allele. These IGF-1Rneo/- mice, strongly deficient in IGF-1R, were subjected to hyperoxia and analyzed for survival time, ventilatory control, pulmonary histopathology, morphometry, lung edema and vascular permeability. Results Strikingly, after 72 h of exposure to 90% O2, IGF-1Rneo/- mice had a significantly better survival rate during recovery than IGF-1R+/+ mice (77% versus 53%, P < 0.05). The pulmonary injury was consistently, and significantly, milder in IGF-1Rneo/- mice which developed conspicuously less edema and vascular extravasation than controls. Also, hyperoxia-induced abnormal pattern of breathing which precipitated respiratory failure was elicited less frequently in the IGF-1Rneo/- mice. Conclusion Together, these data demonstrate that a decrease in IGF-1R signaling in mice protects against oxidant-induced lung injury.

A candidate-gene approach is employed to determine the various mutations taking place in the human ortholog of Chlamydomonas reinhardtii gene with an ODA7 defect. These loss-of-function mutations are shown to be highly responsible for the primary ciliary dyskinesia in humans.

Byline: Rebeca Paiva (1,3,4), Uros Krivec (2,3,4), Guillaume Aubertin (3), Emmanuelle Cohen (4), Annick Clement (3,4), Brigitte Fauroux (3,4) Keywords: Carbon dioxide; Noninvasive positive pressure ventilation; Child; Arterial blood gases Abstract: Introduction Routine monitoring of noninvasive respiratory support relies on nocturnal pulse oximetry and daytime arterial blood gases, without systematic nocturnal carbon dioxide recording. The aim of the study was to assess if overnight pulse oximetry and daytime blood gases are sufficiently accurate to detect nocturnal hypoventilation in children receiving long-term noninvasive respiratory support. Materials and methods Pulse oximetry and carbon dioxide pressure measured by capillary arterialized blood gases and a combined transcutaneous carbon dioxide and pulse oximetry (PtcCO.sub.2/SpO.sub.2) monitor were compared in 65 patients (asthma, n = 16, recurrent bronchitis, n = 8, lung infection, n = 8, cystic fibrosis, n = 15, interstitial lung disease, n = 6, neuromuscular disease, n = 12). Daytime capillary arterialized blood gases and nocturnal recording of pulse oximetry and carbon dioxide by means of a combined PtcCO.sub.2/SpO.sub.2 monitor were performed in 50 other patients receiving nocturnal noninvasive respiratory support at home. Results A correlation was observed between pulse oximetry (r = 0.832, P < 0.0001) and carbon dioxide pressure (r = 0.644, P < 0.0001) measured by capillary arterialized blood gases and the combined PtcCO.sub.2/SpO.sub.2 monitor. Twenty-one of the 50 patients (42%) on long-term noninvasive respiratory support presented nocturnal hypercapnia, defined by a PtcCO.sub.2 value >50 mmHg, without nocturnal hypoxemia. Daytime capillary arterialized carbon dioxide levels were normal in 18 of these 21 patients. Conclusions Nocturnal hypercapnia may occur in children receiving nocturnal noninvasive respiratory support at home. Nocturnal pulse oximetry and daytime arterial blood gases are not sufficiently accurate to diagnose nocturnal hypercapnia, underlying the importance of a systematic carbon dioxide monitoring in children receiving noninvasive respiratory support. Author Affiliation: (1) Pediatric Pulmonary Department, Exequiel Gonzalez Cortes Hospital, Santiago, Chili (2) Unit for Pulmonary Diseases, Division of Pediatrics, University Medical Center, Ljubljana, Slovenia (3) Pediatric Pulmonary Department, AP-HP, Hopital Armand Trousseau, Research Unit INSERM UMR-S 893 Equipe 12, Universite Pierre et Marie Curie-Paris6, 28 avenue du Docteur Arnold Netter, 75012, Paris, France (4) INSERM UMR S-893 Equipe 12, Universite Pierre et Marie Curie-Paris6, Paris, France Article History: Registration Date: 13/01/2009 Received Date: 08/09/2008 Accepted Date: 06/01/2009 Online Date: 27/01/2009