Dramatic impact of morbid obesity on child lung development.

OBJECTIVE: To assess the respiratory function and sleep characteristics of obese adults and children. METHODS: All patients with non-syndromic, severe obesity (BMI ≥3 z-scores for children and ≥40.00kg/m2 for adults), referred for pulmonary function tests at Lille University Hospital, were retrospectively included. RESULTS: A total of 69 children (mean±SD BMI 36.8±6.7 and mean BMI z-score 4.7±1.0) and 70 adults were included (mean BMI 45.7±6.2). Metabolic syndrome was diagnosed in 13 children (26%) and 40 adults (80%). Reduced lung volumes were observed in 34 children (50.0%) and 16 adults (24.0%) and both the mean functional residual capacity (FRC) and the mean residual volume (RV) were lower in children than in adults (FRC: -1.7±2.1 z-score in children vs. -1.0±1.1 in adults, P=0.026; and RV: -0.8±1.2 z-score in children vs. -0.1±1.1 in adults, P=0.002). The prevalence of severe obstructive sleep apnea syndrome was greater in adults (40.7% vs. 18.8%, P=0.007). Children had a higher average oxygen saturation (median of 96.0% [91.0-98.0] vs. 93.0% [76.0-97.0] in adults, P<0.0001). CONCLUSION: Obesity has consequences for lung volumes in children; however, a longitudinal study is needed to determine the impact on pulmonary expansion and growth.

[Lung is also involved in juvenile dermatomyositis]. / Le poumon est une cible de la dermatomyosite de l'enfant.

Juvenile dermatomyositis is the leading cause of chronic idiopathic inflammatory myopathy of auto-immune origin in children. Lung involvement in inflammatory myopathies is well described in adults, involving mostly interstitial lung disease, aspiration pneumonia and alveolar hypoventilation. We propose to describe its specificities in children. Pulmonary involvement may be asymptomatic and therefore must be systematically screened for. In case of clinical or functional respiratory abnormality, a chest computed tomographic (CT) scan is necessary. In children, a decrease of respiratory muscle strength seems common and should be systematically and specifically searched for by non-invasive and reproducible tests (sniff test). Interstitial lung disease usually associates restrictive functional defect, impairment of carbon monoxide diffusion and interstitial lung disease on CT scan. As in adults, the first-line treatment of juvenile dermatomyositis is based on corticosteroids. Corticosteroid resistant forms require corticosteroid bolus or adjuvant immunosuppressive drugs (methotrexate or cyclosporine). There is no consensus in pediatrics for the treatment of diffuse interstitial lung disease. Complications of treatment, including prolonged steroid therapy, are frequent and therefore a careful assessment of the treatments risk-benefit ratio is necessary, especially in growing children.

[Walking tests: a step forward for functional cardiorespiratory assessment]. / Tests de marche: une avancée dans l'évaluation fonctionnelle cardiorespiratoire.

Exercise testing provides information on physical capacity during exercise in addition to spirometric measures of lung function or assessment on treadmills or ergonomic cycle. The "gold standard" assessment of exercise tolerance is measured in the laboratory using treadmills or ergonomic cycle but the necessary equipment is expensive and may not be readily accessible; such tests require people used to work with children. Walking tests are field tests providing a valid and easily accessible method of measuring function-limited exercise tolerance in patients with respiratory or cardiac chronic diseases. These walking tests are non-threatening, inexpensive, easy to perform and to understand for children. Walking tests performed in daily practice are the following: "time-based" tests (2-, 6- or 12-min walking test), 3-min step test (on a step) and the shuttle walking test. It may be a useful measure to assess therapeutic intervention and provide information on the prognosis. They are simple and safe methods to evaluate quality of life in these patients.

Reproducibility of the respiratory dead space measurements in mechanically ventilated children using the CO2SMO monitor.

OBJECTIVES: To assess the reproducibility of respiratory dead space measurements in ventilated children. DESIGN: Prospective study. SETTING: University pediatric intensive care unit. PATIENTS: Thirty-two mechanically ventilated children (0.13-15.4 years) who were clinically stable. METHODS: The single-breath CO(2) test (SBT-CO(2)) was recorded using the CO(2)SMO Plus from the mean of 30 ventilatory cycles during 1 h (at T0, T15, T30, T45, and T60). Airway dead space was determined automatically (Novametrix Medical Systems, USA), and manually by Bohr- Enghoff equations using data obtained by SBT-CO(2). At the end of the study period, arterial blood gas was sampled in order to calculate alveolar and physiologic dead space. Intrasubject reproducibility of measurements was evaluated by the intraclass correlation coefficient. Two-way analysis of variance was used to evaluate the relationships between time and measurements. The two methods for calculating airway dead space were compared by using two-tailed Student's t-test and Bland-Altman analysis. RESULTS: Airway dead space measurement had a good reproducibility during the 1-h period, whatever the method used (intraclass correlation coefficient: 0.84 to 0.87). No significant difference was observed with time. Airway dead space values from the SBT-CO(2) method were smaller than those from Bohr-Enghoff equations. Physiologic dead space values from the SBT-CO2 method were similar to those from Bohr-Enghoff equations. CONCLUSION: The measurement of airway dead space by the CO(2)SMO Plus was reproducible over a 1-h period in children requiring mechanical ventilation, provided ventilatory parameters were constant throughout the study. SBT-CO(2) analysis may provide a bedside non-invasive monitoring of volumetric capnography.

[Reproducibility of the shuttle walk test in children with cystic fibrosis]. / Reproductibilité du test de marche en navette chez des enfants atteints de mucoviscidose.

INTRODUCTION: Exercise testing is useful in the respiratory evaluation of patients with cystic fibrosis. The shuttle walk test (SWT) is a progressive, externally paced, exercise test requiring the subject to walk/run back and forth between two fixed points. The aim is to assess the reproductibility of the SWT in paediatric patients with cystic fibrosis. METHODS: This prospective study recruited 31 children with stable disease. The patients performed two SWT one day (SWT 1 and 2) and two others (SWT 3 and 4) within 15 days. Only SWT 2 and 4 were assessed for reproducibility. RESULTS: 61% were boys, median age (range): 12.9 (7-18.9) years, median Shwachman score (range): 80 (65-100), median values for FEV1 and FVC (range): 92 (55-154) and 92 (64-140)% predicted, respectively. Median distance for SWT 2-4 (range): 910 (580-1020) and 925 (540-1020) metres. Reproducibility for SWT distance and physical activity measured by an accelerometer is very good (intra-class correlation coefficient=0.90 and 0.92, respectively). SWT distance correlated with physical activity (p=3.10(-4)) and weight (p=0.03). SWT distance was independent of the following parameters: height, weight-for-age Z-score, FEV1, FVC, Shwachman score, colonisation with Pseudomonas aeruginosa. CONCLUSIONS: The SWT is reproducible in paediatric patients with cystic fibrosis and provides assessment of respiratory performance that complements spirometric measures of lung function.

[Development of a multiple PCR method for the identification of Ureaplasma parvum and Ureaplasma urealyticum]. / Desarrollo de un método de PCR-múltiple para la identificación de Ureaplasma parvum y Ureaplasma urealyticum.

Ureaplasma parvum and Ureaplasma urealyticum, also known as biovar parvum and biovar T960, respectively, could be associated with several disorders in men, women, and mainly, in newborn children with under weight. Several methods have been developed in order to identify the species or biovars of ureaplasmas. We developed a Multiplex-PCR method using the UPS-UPSA and UUS2-UUA2 primers, specific for U. parvum and U. urealyticum, respectively. This Multiplex-PCR method was used to identify cultures of clinical positive samples to Ureaplasma spp. by the "MYCOFAST Evolution-2" Kit. Of 56 positive cultures to Ureaplasma spp. from newborn children, 70% were U. parvum and 30% U. urealyticum; in 76 positive samples in women, 83% corresponded to U. parvum and 17% to U. urealyticum, while in 63 positive samples of men, 76% identified U. parvum and 24% U. urealyticum. The PCR-multiplex method showed specificity for the identification of the biovars or species of ureaplasmas of clinical interest.

Desarrollo de un método de PCR-múltiple para la identificación de Ureaplasma parvum y Ureaplasma urealyticum. / [Development of a multiple PCR method for the identification of Ureaplasma parvum and Ureaplasma urealyticum]

Ureaplasma parvum and Ureaplasma urealyticum, also known as biovar parvum and biovar T960, respectively, could be associated with several disorders in men, women, and mainly, in newborn children with under weight. Several methods have been developed in order to identify the species or biovars of ureaplasmas. We developed a Multiplex-PCR method using the UPS-UPSA and UUS2-UUA2 primers, specific for U. parvum and U. urealyticum, respectively. This Multiplex-PCR method was used to identify cultures of clinical positive samples to Ureaplasma spp. by the [quot ]MYCOFAST Evolution-2[quot ] Kit. Of 56 positive cultures to Ureaplasma spp. from newborn children, 70

were U. parvum and 30

U. urealyticum; in 76 positive samples in women, 83

corresponded to U. parvum and 17

to U. urealyticum, while in 63 positive samples of men, 76

identified U. parvum and 24

U. urealyticum. The PCR-multiplex method showed specificity for the identification of the biovars or species of ureaplasmas of clinical interest.

Desarrollo de un método de PCR-múltiple para la identificación de Ureaplasma parvum y Ureaplasma urealyticum / [Development of a multiple PCR method for the identification of Ureaplasma parvum and Ureaplasma urealyticum]

Ureaplasma parvum and Ureaplasma urealyticum, also known as biovar parvum and biovar T960, respectively, could be associated with several disorders in men, women, and mainly, in newborn children with under weight. Several methods have been developed in order to identify the species or biovars of ureaplasmas. We developed a Multiplex-PCR method using the UPS-UPSA and UUS2-UUA2 primers, specific for U. parvum and U. urealyticum, respectively. This Multiplex-PCR method was used to identify cultures of clinical positive samples to Ureaplasma spp. by the [quot ]MYCOFAST Evolution-2[quot ] Kit. Of 56 positive cultures to Ureaplasma spp. from newborn children, 70

were U. parvum and 30

U. urealyticum; in 76 positive samples in women, 83

corresponded to U. parvum and 17

to U. urealyticum, while in 63 positive samples of men, 76

identified U. parvum and 24

U. urealyticum. The PCR-multiplex method showed specificity for the identification of the biovars or species of ureaplasmas of clinical interest.

Lung and thorax development during adolescence: relationship with pubertal status.

The aim of the present study was to define reference values for lung volumes and the lung transfer factor for carbon monoxide (TL,CO) for an adolescent population using thoracic volume index (TVI) and an index of pubertal stage in order to account for the variation in growth pattern between adolescents. TVI, pubertal stage by Tanner scale (PST), time since menarche, functional residual capacity measured using the helium-dilution technique, vital capacity, total lung capacity and TL,CO measured using a steady-state method were determined in 51 males (aged 13-20 yrs; PST T3-T5) and 52 females (aged 13-18 yrs; PST T2-T4; all but three had already undergone menarche). In male adolescents, height, weight, TVI, lung volumes and TL,CO increased with age. This was not the case in female adolescents. In males, the TVI was the independent variable that best correlated with pulmonary volumes. In females, height was the independent variable that best correlated with pulmonary volumes. In both sexes, the variable that best correlated with TL,CO was PST, associated with height in males. This cross-sectional study provides prediction equations for lung volumes and the lung transfer factor for carbon monoxide taking into account thoracic volume index and pubertal stage. It shows that, in adolescent males, lung and thoracic development occurs during and until the end of puberty. Conversely, in adolescent females, lung development is almost finished following menarche.

[Multi-parameter indices of weaning from mechanical ventilation in children]. / Indices multi-paramétriques pour le sevrage de la ventilation mecanique chez l'enfant.

UNLABELLED: Simple clinical markers have poor sensitivity; specificity and predictive value in both infants and adults when predicting the success of weaning from mechanical ventilation. Recently, multi-parametric indices, such as the CROP (Compliance-Respiratory Rate-Oxygenation-Pressure) and the RSB (Rapid-Shallow-Breathing) have been used in adults and subsequently in children. The aim of this study was to test the value of the pediatric CROP and RSB (CROPp, RSBp) and the accuracy of a simplified pediatric CROP (CROPpS) that does not require an arterial blood gas sample. MATERIALS AND METHODS: This prospective study was conducted in a pediatric ICU which does not admit neonates. All infants were intubated and ventilated at the time of entry. Spontaneous tidal volume and maximal negative inspiratory pressure, that are required to assess and calculate the indices, were measured using a Fleish pneumotachograph and a unidirectional valve. The other parameters were recorded or calculated. A maximum 4 hour-duration trial of spontaneous ventilation was then performed. Weaning failure was defined as the requirement of re-ventilation within 48 hours of extubation. The discriminant power of CROPp and RSBp was determined by calculating the area under the receiver operating characteristic (ROC) curve. The best cut-off value of the CROPpS was determined by chi2 optimisation. RESULTS: 39 children (20 males) were included in the trial. They had a median age of 3.2 years and a median duration of mechanical ventilation of 1.3 days. 89.7% of children were successfully weaned of mechanical ventilation. Sensitivity of CROP, and RSB, was 97% and 94%, specificity was 0% and 0%, positive predictive value was 89% and 89%, and negative predictive value was 0% and 0% respectively; the area under the ROC curve was 0.57 and 0.74. The CROP,S was found to be as accurate as the CROP, index using the same cut-off value. Comparison of the 2 groups (success, failure) revealed a significant difference in duration of ventilation (longer in the failure group). CONCLUSION: Even though they correctly classified 87% and 85% of patients respectively, the CROPp and RSBp are not good predictors of weaning from mechanical ventilation as the area under the ROC curve is less than 0.80. Other indices need to be evaluated.

Overdistension in ventilated children.

Ventilating patients with acute respiratory failure according to standardized recommendations can lead to varying volume-pressure (V-P) relationships and overdistension. Young children may be more susceptible than adults to overdistension, and individual evaluation of the effects of ventilator settings is therefore required. Three studies have applied indices for the detection of overdistension to dynamic V-P curves in ventilated children. Two of those studies compared these indices to those obtained using a reference technique ([quasi]-static V-P curves), and suggested that the c coefficient of a second order polynomial equation (SOPE) and the ratio of the volume-dependent elastance to total dynamic elastance (%E2) were suitable indices for estimating overdistension.

Ventilator-induced overdistension in children: dynamic versus low-flow inflation volume-pressure curves.

We applied to 20 paralyzed ventilated children (0.15 to 14.3 yr, six with acute respiratory distress syndrome [ARDS]) the low-flow inflation (LFI) technique providing quasi-static volume-pressure (V-P) curves and compared the assessment of overdistension (OD) on dynamic and LFI (reference) inspiratory V-P curves. Dynamic curves were obtained at the airway opening during regular constant flow ventilation (Servo 300). Then LFI curves were obtained. Two analyses were performed: First, the nonlinear coefficient c of a second order polynomial equation (SOPE) fitted to dynamic data obtained during constant flow was compared with the c of SOPE fitted to LFI curve (within tidal volume [VT]). Second, the dynamic C20/C (ratio of compliance of the last 20% of the curve (C20) to total compliance [C]) was compared with the determination of the upper inflection point (UIP) on the LFI curve. OD was defined as a negative value of c, a C20/C < 0.80, an UIP included within the VT range for that child during regular ventilation. Using LFI V-P curves as reference, SOPE offered a better detection of OD than dynamic C20/C or the determination of the UIP by graphical means. Indeed the first analysis showed a substantial agreement (kappa 0.75) between dynamic c and LFI c detection of OD whereas the second analysis showed a poor agreement (kappa 0.22) between C20/ C and LFI detection of the UIP. In conclusion, quasi-static V-P curves can easily be obtained in children with the LFI technique. SOPE offers a good detection of OD on dynamic and LFI V-P curves but the C20/C index seems to be an inadequate measure of OD.

Comparison of four methods for measuring elevation of FRC in mechanically ventilated infants.

The aim of the study was to compare measurements of the elevation of functional residual capacity (FRC) above the relaxation volume obtained in 34 mechanically ventilated infants (median weight 2.6 kg, range 1.2-9) from four different methods: (1) direct measurement of the complete exhalation volume after brief disconnection from the ventilator, (2) calculated measurement from total positive end-expiratory pressure (PEEP) measured by end-expiratory occlusion of the breathing circuit, (3) extrapolated evaluation from the mathematical model of Brody, (4) extrapolated evaluation from the passive expiration method. We considered the direct measurement (1) as the "gold standard". Measurements obtained by total PEEP (2) and by the Brody's mathematical model (3) provided similar results than the direct measurement. Conversely, graphical extrapolation from the passive expiration method (4) underestimated the elevation of FRC. In conclusion, we suggest using the mathematical extrapolation from the Brody's model to evaluate the elevation of FRC in mechanically ventilated infants: this method is non-invasive, does not require disruption of gas flow, can be easily performed with all the neonatal ventilators, and allows continuous breath-by-breath measurements.

Longitudinal clinical and functional pulmonary follow-up after megatherapy, fractionated total body irradiation, and autologous bone marrow transplantation for metastatic neuroblastoma.

BACKGROUND: A prospective follow-up was undertaken to document longitudinal changes in lung function in children with neuroblastoma treated with the Lyon-Marseille-Curie-East of France Group protocol, consisting of high-dose chemotherapy schedules in combination with total body irradiation (TBI) and autologous bone marrow transplantation (ABMT), to determine the extent and timing of any changes seen and to describe late clinical and functional pulmonary sequelae. PROCEDURES: Eighteen children (1.5-6.9 years of age at TBI) performed pulmonary function tests (PFTs). These included measurement of functional residual capacity (FRC) to assess lung growth and dynamic lung compliance (CLdyn) and lung transfer factor for CO (TLCO) for evaluation of distal bronchi and/or interstitial abnormalities. RESULTS: The clinical follow-up showed that bronchopulmonary symptoms occurred in 12 children. Three of them were clinically severely incapacitated. Serial PFTs showed an initial decrease of all mean values 6 months after TBI, with improvement in mean values of FRC and TLCO at 1 year. Thereafter, a significant decrease of mean FRC and CLdyn was observed from 2 years to 4 years after TBI with preservation of TLCO, suggesting restrictive ventilatory defects rather than pulmonary fibrosis. Individual analysis showed PFT defects in 100% of children 4 years after TBI. There was a higher incidence of lung pathology after two blocks of high-dose chemotherapy than after one block (100% versus 40%) and more severe sequelae. However these children had residual disease present after induction associated with lower baseline PFT. CONCLUSIONS: PFT defects were found in all children 4 years after TBI-ABMT, but they remained within acceptable limits except in very young children.

Measurement of respiratory mechanics in paediatric intensive care: in vitro assessment of a pulmonary function device.

OBJECTIVE: To evaluate a recently developed and manufactured device for monitoring respiratory parameters in mechanically ventilated children. DESIGN: In vitro study using a lung model. SETTING: University paediatric intensive care unit. MATERIAL AND INTERVENTIONS: Evaluation of the accuracy of volume and pressure measurements, of the determination of respiratory system compliance (10 to 30 ml/cmH2O) and of resistance (20 and 50 cmH2O/l per s) by the inflation technique (volume- and pressure-controlled mode of ventilation); assessment of interobserver agreement for compliance (10, 15 ml/cmH2O) and resistance (20, 50 cmH2O/l per s) determinations (ANOVA, intraclass correlation coefficient). MEASUREMENTS AND RESULTS: The accuracy of volume measurements (No.1 Fleisch pneumotachograph) was < or = 5 % of true volumes up to 11 (Flow: 30 l/min) even after the introduction of an endotracheal tube. The accuracy of pressure measurements up to 70 cmH2O was < or = 2.5% of the true values. Coefficients of variation of volume and pressure measurements were < 2%. The accuracy of compliance and resistance determinations was, respectively, < or = 17 and 25% of the true values. No significant observer effect was found on compliance and resistance determinations. Indeed, mean differences in compliance and resistance determinations by pairs of observers were < 1%. Intraclass correlation coefficients were > 0.98. CONCLUSIONS: The measuring error of volume, pressure, compliance and resistance determined using this monitoring system seems acceptable for monitoring purpose. Moreover, use of this system by members of the medical team can be recommended since results obtained by observers, even untrained ones, were similar. In vivo evaluation is now needed.

[Isocapnic hyperventilation test adjusted to child's resting ventilation rate]. / Un test d'hyperventilation isocapnique adapté à la ventilation de repos de l'enfant.

In order to validate an Isocapnic Voluntary Hyperventilation (IVH) test applicable to daily practice and to adapt the stimulus to height, 9 healthy and 15 asthmatic children performed a Resting Ventilation Rate (RVR)-corrected IVH. They performed a three-minute IVH with room temperature dry air achieving twice (IVH2) and three times (IVH3) their RVR. Mean Maximal Expiratory Flow (MEF) in the middle half of Forced Vital Capacity (FVC) (MEF25-75%) and mean MEF at 25% of FVC (MEF25%) are decreased in the asthmatic group 10 minutes IVH3 (p = 0.02 and < 0.002) compared to healthy group. Mean FEV1 of both group are not different. Comparing Forced Expiratory Flows variation after IVH to baseline intrasubject coefficient of variation, sensitivity of the test is 80% and specificity 100% when variations of MEF25-75% and MEF25% together with FEV1 variations are considered. This suggests an easy way to adapt an hyperventilation stimulus to size and emphasizes the utility of taking account of MEF25-75% and MEF25% in detecting non specific bronchial hyperreactivity in asthmatic children.

[Asthma in infants. Clinical and functional aspects]. / Asthme du nourrisson. Aspects cliniques et fonctionnels.

BACKGROUND: The incidence of asthma in infancy is rising but its clinical and physiological components remain unclear. METHODS: A total of 24 infants, aged less than 48 months, in whom the first wheezing episode (WE) appeared before the age of 30 months (mean age: 9 months) underwent clinical examination and pulmonary function tests at least 2 weeks after the last WE. RESULTS: The mean WE frequency was 1.1 per month and the mean number of admissions for WE was 1.8. 63% of patients showed symptoms between WE and 50% had an allergic profile. There was no evidence of thoracic distension. Bronchial obstruction (BO) occurred in 71% of patients; among these, BO was distal or generalized in 59% and medium or severe in 47%. 12.5% of patients were hypoxemic at testing. BO was less severe in patients treated with theophylline; it was more frequent (87%) in those with symptoms between WE and/or several admissions, and/or admission to the intensive care unit. CONCLUSION: This study provides additional evidence that infants presenting with asthma at an early age have severe clinical and physiological profiles.