Whole pulmonary assessment 1 year after paediatric acute respiratory distress syndrome: prospective multicentre study.

BACKGROUND: Long-term pulmonary sequelae, including 1-year thoracic computed tomography (CT) sequelae of paediatric acute respiratory distress syndrome (ARDS) remain unknown. The purpose of the study was to determine pulmonary abnormalities in child survivors of pulmonary (p-ARDS) and extra-pulmonary ARDS (ep-ARDS) 1 year after paediatric intensive care unit discharge (PICUD). METHODS: Prospective multicentre study in four paediatric academic centres between 2005 and 2014. Patients with ARDS were assessed 1 year after PICUD with respiratory symptom questionnaire, thoracic CT and pulmonary function tests (PFT). RESULTS: 39 patients (31 p-ARDS) aged 1.1-16.2 years were assessed. Respiratory symptoms at rest or exercise and/or respiratory maintenance treatment were reported in 23 (74%) of children with p-ARDS but in 1 (13%) of those with ep-ARDS. Thoracic CT abnormalities were observed in 18 (60%) of children with p-ARDS and 4 (50%) of those with ep-ARDS. Diffuse and more important CT abnormalities, such as ground glass opacities or mosaic perfusion patterns, were observed in 5 (13%) of children, all with p-ARDS. PFT abnormalities were observed in 30 (86%) of patients: lung hyperinflation and/or obstructive pattern in 12 (34%) children, restrictive abnormalities in 6 (50%), mild decrease in diffusing capacity in 2 (38%) and 6-min walking distance decrease in 11 (73%). Important PFT abnormalities were observed in 7 (20%) children, all with p-ARDS. Increasing driving pressure (max plateau pressure-max positive end-expiratory pressure) was correlated with increasing CT-scan abnormalities and increasing functional residual capacity (more hyperinflation) (p < 0.005). CONCLUSIONS: Children surviving ARDS requiring mechanical ventilation present frequent respiratory symptoms, significant CT-scan and PFT abnormalities 1 year after PICUD. This highlights the need for a systematic pulmonary assessment of these children. Trial registration The study was registered on Clinical Trials.gov PRS (ID NCT01435889).

Quality of life was similar in children with congenital diaphragmatic hernia and oesophageal atresia and related to respiratory morbidity.

AIM: To assess quality of life (QoL) in children with congenital diaphragmatic hernia (CDH) and to compare it with oesophageal atresia (OA). METHODS: A cross-sectional study in CDH children (≥7 years) was conducted in Lille University Hospital, France, from January 2013 to April 2014. History, lung function (rest, exercise) and Pediatric Quality of Life Inventory questionnaires (PedsQoL 4.0) were collected. Data of OA children were previously published. RESULTS: Fifty-four CDH patients (male: 53%, median age: 11 years, IQR 9-14) were compared to 54 OA patients (male: 61%, median age: 13 years, IQR: 11-15). CDH children had significantly more frequent history of pneumonia (30% vs 13%), exercise limitation (54% vs 35%) and chest deformity (39% vs 11%); 46% had an obstructive pattern and 66% an abnormal cardiopulmonary exercise test. The median PedsQoL total score in children was 81 (IQR 73-90) in CDH and 81 (IQR 72-91) in OA (P = .8). In CDH, duration of neonatal oxygen therapy, hospitalisation for respiratory disease, exercise limitation, inhaled corticosteroids treatment, chest deformity, abnormal cardiopulmonary exercise test and lower forced expiratory volume in one second were significantly associated with lower QoL scores. CONCLUSION: PedsQoL scores remained satisfactory in CDH children with CDH, with no difference compared to OA. Patients with respiratory morbidity and lung function impairment, who displayed lower scores, should be identified in order to optimise their management in reference centres.

Global Lung Initiative spirometry references in healthy 3-15-year-old French children.

Global Lung Initiative spirometry references satisfactorily fit data of healthy 3- to 15-year-old French children http://bit.ly/2Z2922R.

Virus-triggered exacerbation in allergic asthmatic children: neutrophilic airway inflammation and alteration of virus sensors characterize a subgroup of patients.

BACKGROUND: Viruses are important triggers of asthma exacerbations. They are also detected outside of exacerbation. Alteration of anti-viral response in asthmatic patients has been shown although the mechanisms responsible for this defect remain unclear. The objective of this study was to compare in virus-infected and not-infected allergic asthmatic children, aged 6 to 16 years, admitted to hospital for a severe exacerbation, the innate immune response and especially the expression of pattern recognition receptor (PRR) and their function. METHODS: Virus identification was performed both during the exacerbation and at steady state (eight weeks later). Data assessed at both periods included clinical features, anti-viral response and inflammation (in sputum and plasma), and PRR expression/function in blood mononuclear cells. RESULTS: Viruses were identified in 46 out of 72 children (median age 8.9 years) during exacerbation, and among them, in 17 at steady state. IFN-ß, IFN-γ and IL-29 levels in sputum and plasma were similar between infected and not infected patients at both times, as well as the expression of TLR3, RIG-I and MDA5 in blood monocytes and dendritic cells. Airway inflammation in infected patients was characterized by significantly higher IL-5 concentration and eosinophil count. Compared to patients only infected at exacerbation, the re-infected children significantly exhibited lower levels of IFN-γ in plasma and sputum at exacerbation associated with modifications in PRR expression and function in blood mononuclear cells. These re-infected patients also presented an airway neutrophilic inflammation at steady state. CONCLUSION: Our results reports in asthmatic children that impaired anti-viral response during virus-induced exacerbation is more pronounced in a subgroup of patients prone to re-infection by virus. This subgroup is characterized by altered PRR function and a different pattern of airway inflammation. TRIAL REGISTRATION: This multicenter prospective study was approved by the regional investigational review board (ref: 08/07).

Utility of measuring FEV0.75/FVC ratio in preschoolers with uncontrolled wheezing disorder.

Uncontrolled wheezing disorder is common in preschoolers and disease control assessment is challenging as parents frequently overestimate the extent to which their child's disease is controlled. This is the first study of forced expiratory volume in t s (FEVt)/forced vital capacity (FVC) ratio measurements (i.e. FEV1/FVC, FEV0.75/FVC and FEV0.5/FVC) in wheezy preschoolers in relation to disease control. Our objective was to evaluate whether FEVt/FVC ratios less than the lower limit of normal (LLN; z-score <-1.64) were associated with uncontrolled wheezing disorder in preschoolers.Valid FVC, FEV1, FEV0.75 and FEV0.5 values were obtained in 92 healthy and 125 wheezy (62% uncontrolled) children (3-5 years). Associations between spirometry value

Bevacizumab decreases vestibular schwannomas growth rate in children and teenagers with neurofibromatosis type 2.

Vestibular schwannoma (VS) growth in neurofibromatosis type 2 (NF2) can be responsible for brainstem compression and hearing loss. Surgical removal remains the standard therapy despite potential morbidity. Previous studies suggested that the inhibition of the VEGF-pathway with bevacizumab could result in hearing improvement, reduction of the tumor volume or both in adults. We retrospectively describe the French experience of bevacizumab treatment delivered for progressive VS in pediatric NF2 patients. Patients received Bevacizumab 5 or 10 mg/kg every 2 weeks according to the physician's choice. Follow-up included clinical assessment, audiometry and volumetric MRI every 3-6 months. Seven patients harboring 11 VS were included. The median age at inclusion was 15 years (11.4-18.8), and the median treatment duration was 11.3 months (3.2-55.6). At baseline, the median tumor volume was 1.2 cm(3) (0.52-13.5) and the median word recognition score was 90 % (0-100). We observed one major response, two minor responses and a decrease in the rate of tumor growth for the 4 other patients. The median annual growth rate before treatment was significantly higher than after 1 year of treatment (138 vs. 36 %, n = 5, p = 0.043). We noted one hearing improvement over the course of 1 year under treatment (hearing response rate was 14 %). Overall, the treatment was well tolerated. Our study supports that bevacizumab is an attractive therapeutic option for pediatric NF2 patients with growing VS. Thorough multidisciplinary evaluation is necessary to identify the best candidates prior to treatment. It is likely that a better functional outcome would be expected if targeted therapies were discussed early in the management of the disease.

Reference ranges for shape indices of the flow-volume loop of healthy children.

BACKGROUND: The concavity of the descending limb of the maximum expiratory flow-volume loop (MEFVL) is the earliest change associated with airflow obstruction in small airways (ATS/ERS Task Force). The shape of the MEFVL changes with age but there are no reference values for shape indices for preschool and school children. OBJECTIVES: To define pediatric reference values for spirometric data and 3 shape indices of MEFVL: 2 geometric indices: the ß angle i.e., the angle between the first ½ part and the 2nd part of the MEFVL and the forced expiratory flow after 50% of the forced vital capacity (FVC) has been exhaled/peak expiratory flow (FEF50 /PEF) ratio; and a ratio that describes relative growth between airway and lung parenchyma, the forced expiratory flow between 25 and 75% of FVC/FVC ratio (FEF25-75 /FVC ratio). METHODS: Data were obtained from 446 Caucasian children (2.5 to 15-year-old). The lambda, mu, sigma method was applied. RESULTS: References for spirometric parameters and 3 shape indices. The geometric indices decreased with age from 3 years of age (mean ß angle was 215° and FEF50 /PEF ratio was 0.82) until 8 years of age (mean ß angle was 191° and FEF50 /PEF ratio was 0.60) and then remained constant. The FEF25-75 /FVC ratio also decreased with age. Sex was a significant determinant for FEF25-75 /FVC ratio predicted values. CONCLUSIONS: This study provides standard reference equations for indices of mid-expiratory flows in children and we suggest using the FEF50 /PEF index.

The lung is involved in juvenile dermatomyositis.

BACKGROUND: Juvenile dermatomyositis (JDM) is the main cause of chronic idiopathic inflammatory myopathy of autoimmune origin in children. The aim of this multicenter prospective study was to describe respiratory status and treatment of children followed for JDM. METHODS AND PATIENTS: Clinical manifestations, pulmonary function tests (PFT), chest high-resolution computed tomography (HRCT) scan results, and treatments and their adverse effects were analyzed in children followed for JDM. RESULTS: Twenty-one patients (median age: 9.9 years; range: 20 months-18 years) were included. The median of disease duration at the time of the analysis was 3 years (range: 6 months-9 years 4 months). Overall 16 (76%) of 21 children presented with a respiratory involvement related to JDM including interstitial lung disease (n = 3) and/or respiratory muscle involvement (n = 7). Seven patients presented with other nonspecific manifestations. Three children had aspiration pneumonia. A chest HRCT was performed in 15 children, and abnormalities were observed in 12. PFT were performed in 20 of 21 patients. Seven showed functional abnormalities: restrictive ventilatory defect (n = 3) or obstructive ventilatory defect (n = 4). Six patients had abnormal respiratory muscle tests, including three with a restrictive ventilatory defect and one with an obstructive ventilatory defect. One other child with an acute aspiration pneumonia had a clearly muscle respiratory involvement but was too young to perform respiratory muscle tests and confirm this diagnosis. Treatment comprised systemic corticosteroid for all patients and adjuvant immunosuppressive therapy for 11. Adverse effects linked to treatment were reported in eight patients. CONCLUSION: The frequency of lung involvement in children with JDM justifies systematic respiratory assessment with PFT including measures of respiratory muscle strength. We suggest that a chest HRCT scan is indicated in cases of respiratory symptoms and/or PFT abnormalities. Longitudinal studies are needed to assess pediatric characteristics, long-term outcomes, and responses to treatment taking into account the risk-benefit ratio.

Sniff nasal inspiratory pressure in the longitudinal assessment of young Duchenne muscular dystrophy children.

Traditional measures of respiratory function in children with Duchenne muscular dystrophy (DMD) are based on maximal inspiratory pressure (PImax) and vital capacity (VC). Sniff nasal inspiratory pressure (SNIP) measurements are easily performed by young children with neuromuscular disorders. The clinical value of SNIP in the longitudinal assessment of respiratory weakness remains to be assessed. The objective of the present study was to assess longitudinally the changes in SNIP, PImax and VC with age in DMD children. We hypothesised that their longitudinal assessment would show an earlier decline in SNIP than VC. A 3-year, prospective follow-up, at 6-month intervals of, 33 steroid-naïve, 5-20-year-old DMD patients was analysed using a linear mixed model. SNIP measurements were reliable (within-session coefficient of variation 8%). SNIP and VC increased until 10.5 and 12.5 years of age, respectively, and declined thereafter, while PImax did not change with age. SNIP was an earlier marker of decline in respiratory muscle strength (at 10.5 years) than VC (at 12.5 years) in young DMD patients. SNIP longitudinal assessment is useful in the detection of inspiratory strength decline in young DMD patients when VC values remain within normal values and as an outcome measure in clinical trials for emerging therapeutics in young DMD patients from the age of 5 years.

Quantification of shape of flow-volume loop of healthy preschool children and preschool children with wheezing disorders.

BACKGROUND: The earliest change associated with airflow obstruction in small airways is reflected in a concave shape on the maximum expiratory flow-volume loop (MEFVL). The shape of the MEFL changes with age but reference values for curvilinearity indices (CI) for preschool children have not been published. We aimed to describe the normal curvilinearity of healthy preschool MEFVL by CI (the ß angle and the ratio of maximum expiratory flow when 50% of forced vital capacity remains to be expired/peak expiratory flow (MEF(50%) /PEF)) and to test their capacity in detecting concavity in preschool children with wheezing disorders. METHODS: Spirometric data were obtained from 132 healthy preschool children and 171 3-to-5-year-old preschool children with wheezing disorders and reference values for CI calculated. RESULTS: Mean (SD) ß angle of healthy children was 203° (16°) and mean MEF(50%) /PEF of healthy children was 0.71 (0.12) indicating convexity of MEFVL, both decreased with increasing age (P = 10(-4) ). Children with wheezing disorders had lower z-score values of CI (P ≤ 10(-6) ) indicating more concave MEFVL. Among the two CI, MEF(50%) /PEF allowed for the best discrimination between healthy children and children with wheezing disorders (Wilks' lambda = 0.898, P = 10(-7) ). CONCLUSION: These CI can detect and quantify the concavity of the descending limb of the MEFVL in preschool children with wheezing disorders, MEF(50%) /PEF having the highest sensitivity in detecting the concavity.

Natural evolution of weight status in Duchenne muscular dystrophy: a retrospective audit.

The life expectancy of patients with Duchenne muscular dystrophy (DMD) has increased. A cross-sectional study of DMD patients showed that 54 % of 13-year-old patients are obese and that 54 % of 18-year-old patients are underweight. We aimed to describe the natural evolution of weight status in DMD. This retrospective multi-centre audit collected body-weight measurements for seventy DMD patients born before 1992. The body-weight:age ratio (W:A) was used to evaluate weight status in reference to the Griffiths and Edwards chart. At the age of 13 years, 73 % were obese and 4 % were underweight. At maximal follow-up (age 15-26 years, mean 18·3 (sd 2·3) years), 47 % were obese and 34 % were underweight. Obesity at the age of 13 years was associated with later obesity, whereas normal weight status and underweight in 13-year-old patients predicted later underweight. A W:A ≥ 151 % in 13-year-old patients predicted later obesity, and a W:A ≤ 126·5 % predicted later underweight. Our audit provides the first longitudinal information about the spontaneous outcome of weight status in DMD. Patients (13 years old) with a W:A ≥ 151 % were more likely to become obese in late adolescence, but obesity prevented later underweight. These data suggest that mild obesity in 13-year-old DMD patients (W:A between 120 and 150 %) should not be discouraged because it prevents later underweight.

Effects of inertance on respiratory mechanics measurements in mechanically ventilated children.

OBJECTIVE: The use of the first-order linear single compartment model when studying respiratory mechanics classically neglects inertance (Irs). We hypothesized that Irs would affect compliance (Crs) and resistance (Rrs) estimates in mechanically ventilated young children. DESIGN: Prospective study; single-center evaluation. SETTING: University-affiliated tertiary pediatric intensive care unit. PATIENTS: Forty-four patients with and without respiratory disease. INTERVENTIONS: Patients were studied during volume-controlled constant inspiratory flow ventilation. MEASUREMENTS AND MAIN RESULTS: Pressure (PaO) and flow (V') were analyzed according to two different models: a one-compartment first-order linear model according to PaO = (1/Crs) x V + Rrs x V' and a one-compartment second-order linear model according to PaO = (1/Crs) x V + Rrs x V' + Irs x V''. Irs was higher in children with vs. those without respiratory disease (median 0.00224 cm H2O/L/sec2, Q1-Q3 0.00180-0.00321 vs. median 0.00133 cm H2O/L/sec2, Q1-Q3 0.00072-0.00210; p < .001)). A positive correlation between Irs and the difference of Crs estimates between the first- and the second-order model was found in both groups (r = .84, p < .05 and r = .67, p < .05). Rrs estimates were similar in both groups. CONCLUSIONS: This study showed that the linear single-compartment model may not adequately estimate the respiratory mechanical properties in mechanically ventilated children, particularly in the presence of respiratory disease. Including an Irs term significantly diminished Crs estimates. A one-compartment second-order linear model might be a useful clinical tool in more adequately measuring respiratory mechanics and optimizing ventilatory settings in children with respiratory disease.

Spirometry in 3-5-year-old children with asthma.

Spirometry with incentive games was applied to 207 2-5-year-old preschool children (PSC) with asthma in order to refine the quality-control criteria proposed by Aurora et al. (Am J Respir Crit Care Med 2004;169:1152-159). The data set in our study was much larger compared to that in Aurora et al. (Am J Respir Crit Care Med 2004;169:1152-159), where 42 children with cystic fibrosis and 37 healthy control were studied. At least two acceptable maneuvers were obtained in 178 (86%) children. Data were focused on 3-5-year-old children (n = 171). The proportion of children achieving a larger number of thresholds for each quality-control criterion (backward-extrapolated volume (Vbe), Vbe in percent of forced vital capacity (FVC, Vbe/FVC), time-to-peak expiratory flow (time-to-PEF), and difference (Delta) between the two FVCs (DeltaFVC), forced expiratory volume in 1 sec (DeltaFEV(1)), and forced expiratory volume in 0.5 sec (DeltaFEV(0.5)) from the two "best" curves) was calculated, and cumulative plots were obtained. The optimal threshold was determined for all ages by derivative function of rate of success-threshold curves, close to the inflexion point. The following thresholds were defined for acceptability: Vbe

Evaluation of a noninvasive cardiac output monitor in mechanically ventilated children.

OBJECTIVE: To compare measurements of cardiac output (CO) and cardiac index (CI) obtained by a recently developed noninvasive continuous cardiac output system, NICO (CONICO), and transthoracic Doppler echocardiography (COTTE) in mechanically ventilated children. DESIGN AND SETTING: Prospective study in a university-affiliated tertiary pediatric intensive care unit. PATIENTS: A total of 21 mechanically ventilated children, weighing >15 kg, in stable respiratory and hemodynamic condition. MEASUREMENTS: Sets of three successive measurements of CO with the NICO system and transthoracic Doppler echocardiography were obtained. Bland-Altman analysis was used to compare the agreement between the two methods. RESULTS: The mean +/- sd CO values were 4.06 +/- 1.43 L/min for CONICO and 4.67 +/- 1.78 L/min for COTTE. Bias +/- sd between the two methods was -0.61 +/- 0.94 L/min. The variability of the difference between the two methods increased as the magnitude of the CO measurement increased. Similar results were obtained for cardiac index: 4.01 +/- 1.40 L.min.m for CINICO and 4.59 +/- 1.48 L.min.m for CITTE. Bland-Altman analysis revealed a nonuniform relationship between CI difference and the magnitude (y = -0.299 - 0.0655 x mean). The variability of the differences did not increase as the magnitude of the CO measurement increased (sd of estimate was 0.827 L.min.m). With both CONICO and CINICO, each measurement was highly repeatable, with coefficient of variation of only 2.88% +/- 2.31%. Repeatability with Doppler echocardiography was 7.02% +/- 4.33%. CONCLUSIONS: The NICO system is a new device that measures CO easily and automatically in mechanically ventilated children weighing >15 kg. CO values obtained with this technique were in agreement with those obtained with Doppler echocardiography in children in respiratory and hemodynamic stable condition. The NICO system needs further investigation in children in unstable respiratory and hemodynamic condition.

Influence of respiratory system impedance on volume and pressure delivered at the Y piece in ventilated infants.

OBJECTIVES: Tidal volume (VT) delivered to infants' airways are overestimated and pressure underestimated when measured in the ventilator and not at the Y piece. This study aimed at evaluating the influence of respiratory system impedance on expiratory VT (VTE) and pressure measurement difference. DESIGN: Prospective observational study. SETTING: Pediatric intensive care unit at a university hospital. PATIENTS: Data were collected between February 2000 and October 2001 for 30 infants (range, 1-23 months) ventilated in the pressure-controlled or volume-controlled mode. INTERVENTIONS: Measurements of VTE, pressure obtained at the same time at the Y piece and on the ventilator Servo 300, were collected in ventilated infants. Respiratory system impedance was calculated from data obtained at the Y piece. Circuit compliance was measured in vitro. VTEs were corrected for compressible volume. MEASUREMENTS AND RESULTS: VTEs were overestimated by the Servo 300 in the pressure-controlled and volume-controlled modes (from 5% to 62% of the value displayed on Servo 300). Maximal inspiratory pressures were underestimated by the Servo 300 in the pressure-controlled mode (difference from -2 to +19 cm H(2)O). Measurement difference increased with increasing respiratory system impedance. Ventilator VTE corrected for circuit compliance did not offer a sufficiently accurate estimation of VTE at the Y piece. CONCLUSIONS: VT and pressure measurements must be performed at the Y piece, especially in infants with increased respiratory system impedance (i.e., decreased respiratory system compliance or increased resistance). Correcting VTE for circuit compliance cannot replace measurement of VT at the Y piece.

Effect of increasing inspiratory time on respiratory mechanics in mechanically ventilated neonates.

OBJECTIVE: To investigate the effect of inspiratory time and inspiratory flow on the respiratory mechanics of intubated and ventilated neonates. DESIGN: Physiology study. SETTING: Tertiary university neonatal intensive care unit. PATIENTS: Neonates requiring mechanical ventilation with (group 1, n = 9) and without lung disease (group 2, n = 6). INTERVENTIONS: All infants were ventilated with a Servo 900C Siemens ventilator in the volume-controlled constant-flow mode. Flow and pressure were measured at the Y-piece, while different inspiratory times (25%, 33%, 50%, and 67% of the respiratory cycle) were applied randomly without changing tidal volume. MEASUREMENTS: The constant flow end-inspiratory airway occlusion technique allowed partitioning of the total respiratory system resistance (R(tot,rs)) into a standard intrinsic flow resistance (R(int,rs)) and a lung/thorax tissue viscoelastic component (DeltaR(rs)), and it allowed partitioning of the dynamic respiratory system elastance (E(dyn,rs)) into a static (E(st,rs)) and a lung/thorax tissue viscoelastic component (DeltaE(rs)). A two-compartment model of the respiratory system was applied to the experimental data. MAIN RESULTS: All respiratory mechanics components were significantly higher in group 1 compared with group 2. Both groups showed increasing R(int,rs) with increasing flow and increasing DeltaR(rs) with increasing inspiratory time. DeltaR(rs) represented 40% to 75% of R(tot,rs) whatever the group. E(dyn,rs) and E(st,rs) changed with inspiratory time in the very low (<0.4 secs) and the very long inspiratory time range (>1.0 secs). No change was found when clinically, commonly used inspiratory times were applied (0.4-1.0 secs). DeltaE(rs) represented 17% to 19% of E(dyn,rs). The relationship between DeltaR(rs) and increasing inspiratory time fitted the exponential two-compartment model (r =.99, p <.001). CONCLUSIONS: Total respiratory mechanics and its components in ventilated newborns with and without lung disease showed inspiratory time dependence. DeltaR(rs) increased with increasing inspiratory time as predicted by the two-compartment lung model, whereas standard R(int,rs) and E(dyn,rs) decreased.