Baseline and post-bronchodilator interrupter resistance and spirometry in asthmatic children.

In children unable to perform reliable spirometry, the interrupter resistance (R(int) ) technique for assessing respiratory resistance is easy to perform. However, few data are available on the possibility to use R(int) as a surrogate for spirometry. We aimed at comparing R(int) and spirometry at baseline and after bronchodilator administration in a large population of asthmatic children. We collected retrospectively R(int) and spirometry results measured in 695 children [median age 7.8 (range 4.8-13.9) years] referred to our lab for routine assessment of asthma disease. Correlations between R(int) and spirometry were studied using data expressed as z-scores. Receiver operator characteristic curves for the baseline R(int) value (z-score) and the bronchodilator effect (percentage predicted value and z-score) were generated to assess diagnostic performance. At baseline, the relationship between raw values of R(int) and FEV(1) was not linear. Despite a highly significant inverse correlation between R(int) and all of the spirometry indices (FEV(1) , FVC, FEV(1) /FVC, FEF(25-75%) ; P < 0.0001), R(int) could detect baseline obstruction (FEV(1) z-score ≤ -2) with only 42% sensitivity and 95% specificity. Post-bronchodilator changes in R(int) and FEV(1) were inversely correlated (rhô = -0.50, P < 0.0001), and R(int) (≥35% predicted value decrease) detected FEV(1) reversibility (>12% baseline increase) with 70% sensitivity and 69% specificity (AUC = 0.79). R(int) measurements fitted a one-compartment model that explained the relationship between flows and airway resistance. We found that R(int) had poor sensitivity to detect baseline obstruction, but fairly good sensitivity and specificity to detect reversibility. However, in order to implement asthma guidelines for children unable to produce reliable spirometry, bronchodilator response measured by R(int) should be systematically studied and further assessed in conjunction with clinical outcomes.

[Malnutrition in children with chronic bronchitis]. / Prévalence et conséquences de la dénutrition au cours de la bronchite chronique de l'enfant.

OBJECTIVE: To study nutritional status in children with chronic bronchitis (CB) in relation with lung function. METHODS: In this cohort of study, 46 patients aged 6.0 to 17.5 years (mean: 11.9 years) with chronic bronchitis were recruited. None had cystic fibrosis. Body weight, height, skinfold thicknesses, percentage of ideal body weight-for-height (percentage of IBW), body mass index (BMI), BMI Z-score, fat mass and fat-free mass were used to evaluate nutritional status. Arterial blood gases, vital capacity (VC), forced expiratory volume in one s (FEV1), functional residual capacity (FRC) and maximum inspiratory (Pi(max)) and expiratory (Pe(max)) pressures at the mouth were used to evaluate respiratory function. RESULTS: Thirteen children (28%) had malnutrition defined as percentage of IBW lower than 90%, with a predominant fat mass depletion. VC (65+/-13% versus 79+/-15%; p=0.006) and FEV1 (59+/-16% versus 69+/-14%; p=0.03) were significantly lower in children with malnutrition than in children without malnutrition, but no significant differences were observed with regard to the FEV1/VC ratio and blood gases. Pi(max) (56+/-11% versus 88+/-37%, p=0,02) and Pe(max) (46+/-12% versus 58+/-19%, p=0,3) were also lower in children with malnutrition as compared to than without malnutrition. CONCLUSION: Malnutrition can be observed in children with CB and is associated with significant lower lung function parameters. This could be explained by decrease in respiratory muscle strength.

[Methacholine challenge in young children: measurement of resistance by interruption]. / Test a la métacholine chez le jeune enfant: Mesure de la résistance par interruption.

The aims of this study were 1. To evaluate the measurement of resistance by interruption (Rint) of bronchoconstriction induced by inhalation of methacholine and 2. To determine a threshold of increase of resistance in young children to differentiate responders from non-responders. Forty-six children (mean age 5 [4.3-6.1] years) referred for methacholine challenge were tested by measurement of Rint and transcutaneous oxygen tension. A fall of 20% or more in oxygen tension from the baseline was used to define the responders. The children studied had a baseline Rint significantly higher than normal (0.84 [0.68-1.01] vs. 0.76 [0.60-0.90] kPa L(-1)s; p < 0.03). Forty-one children were responders and had an increase in Rint significantly different from the non-responders (p < 0/04). An increase in Rint of 35% distinguished responders from non-responders in young children with chronic cough. Interrupter resistance increases significantly during bronchial provocation in responding young children and may be used to measure the degree of bronchoconstriction.

[Diseases of the pulmonary lymphatic system in children]. / Pathologies des lymphatiques pulmonaires chez l'enfant.

Diseases of the lymphatic system in children include a group of exceptional conditions difficult to manage. The anatomy of lymphatic system is complex in the lung. Variable from one subject to another, its complex physiology plays an important role in air-blood exchanges occurring in the lung. In the pulmonary interstitium and in the pleura, the lymphatic system acts like an overflow valve capable of regulating variations in interstitial fluid. The presence or development of dysplasic lymphatics causes leakage, dilatation, and reflux of the lymph through incontinent valves leading to chylothorax and/or fluid overload in the pulmonary interstitium. Symptomatic care is usually proposed, based on a fat-free diet supplemented with light-chain triglycerides and liposoluble vitamins. Other therapeutic options can be proposed. Medical options include cytotoxic agents, somatostatin, and interferon-alpha. Surgery may also be useful, but an assessment of therapeutic efficacy is very difficult due to partial effects and the small number of cases studied.

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.

Chronic stridor caused by laryngomalacia in children: work of breathing and effects of noninvasive ventilatory assistance.

Breathing pattern, gas exchange, and respiratory effort were assessed in five awake children with chronic stridor caused by laryngomalacia during spontaneous breathing (SB) and noninvasive mechanical ventilation (NIMV). During SB, the youngest children were able to maintain normal gas exchange at the expense of an increased work of breathing as assessed by calculated diaphragmatic pressure-time product (PTPdi), whereas the opposite was observed in the older children. NIMV increased tidal volume, from 8.77 +/- 2.04 ml/kg during SB to 11.67 +/- 2.52 ml/kg during NIMV, p = 0.04, and decreased respiratory rate, from 24.4 +/- 5.6 breaths/ min during SB to 16.6 +/- 0.9 breaths/min during NIMV, p = 0.04. NIMV unloaded the respiratory muscles as reflected by the significant reduction in PTPdi, from a mean value of 541.0 +/- 196.6 cm H(2)O x s x min(-1) during SB to 214.8 +/- 116.0 cm H(2)O x s x min(-1) during NIMV, p = 0.04. Therefore, NIMV successfully relieves the additional load imposed on the respiratory muscles. Long-term home NIMV was provided to a total of 12 children with laryngomalacia (including these five) and was associated with clinical improvement in sleep and growth.

Abnormal central complex is a marker of severity in the presence of partial ciliary defect.

BACKGROUND: Ciliary ultrastructural defects with total lack of dynein arms (DA) cause abnormal mucociliary function leading to the chronic infections observed in primary ciliary dyskinesia. The role of partial ciliary ultrastructural defects, especially those involving the central complex, and their relationship with respiratory symptoms have been less thoroughly investigated. OBJECTIVE: In a pediatric population with partial ciliary defects, we determined the relationship(s) between ultrastructural findings, ciliary motility, and clinical and functional features, and evaluated the outcome of this population. DESIGN: We analyzed the clinical presentation and pulmonary function of 43 children with chronic bronchitis and partial ultrastructural defects (from 15% to 90%) of their respiratory cilia demonstrated on bronchial biopsies. The study population was divided into 3 groups according to ciliary ultrastructure: the main ultrastructural defect concerned the central complex in 23 patients (CC group), peripheral microtubules in 8 patients (PMT group), and DA in 12 patients (DA group). RESULTS: The percentage of ciliary defects was lower in the PMT group than in the CC and DA groups. Patients in the PMT group had less severe disease with frequent normal ciliary motility. Patients in the CC group had initially a higher incidence of respiratory tract infections, extensive bronchiectasis frequently requiring surgery, and arguments in favor of a congenital origin (high proportion of sibling form). Partial absence of DA, although of congenital origin, was associated with a good prognosis. In all groups, follow-up showed that the functional prognosis remained good with appropriate treatment. CONCLUSIONS: In children with chronic respiratory infections, presence of situs inversus, sibling form, obstructive pulmonary syndrome, or bronchiectasis required ultrastructural analysis, regardless of ciliary motility. Detection of CC abnormalities is a marker of severity and required intensive therapy and close follow-up.

Pulmonary sarcoidosis in children: a follow-up study.

Progression of pulmonary sarcoidosis in children remains poorly documented. The aim of this work was to gather follow-up information on pulmonary outcomes in children with sarcoidosis and to obtain data of relevance to a discussion of the optimal length and regimen of glucocorticoid therapy. In the present study, the authors experience of pulmonary sarcoidosis in 21 children referred to the paediatric pulmonary department over a 10-yr period is reported with a documented follow-up of at least 4 yr. Evaluation of the disease during the follow-up included analysis of clinical manifestations, chest radiographs, pulmonary function tests with measurements of the vital capacity (VC), dynamic lung compliance (CL,dyn), lung transfer for CO (TL,CO), and arterial blood gases, as well as bronchoalveolar lavage (BAL) with determination of total and differential cell counts. After initial evaluation the decision was a careful observation of four children without therapy. Corticosteroid treatment was initiated in 17 children. Analysis of results indicated that after 6-12 months of treatment most clinical manifestations of the disease and chest radiograph abnormalities disappeared, and beneficial effects on VC and TL,CO were apparent. After 18 months of steroids no benefit on pulmonary function tests could be noticed, with mainly persistence of alterations of CL,dyn. Results of BAL studies documented the presence of an alveolitis with increased lymphocyte populations throughout the follow-up. Relapses were observed in four children during tapering of prednisone; they were not reported after discontinuation of steroid therapy. Taken together data obtained in the presented population can lead to the following suggestions for the management of pulmonary sarcoidosis in children. BAL should be performed at the initial evaluation to document alveolitis; however, nothing seems to be gained from repeating this investigation during follow-up in the absence of specific reasons. Once the decision to initiate glucocorticoid therapy is made, 18 months may be a reasonable treatment duration. Discontinuation of therapy can be decided even if the pulmonary function tests remain abnormal, but the child should then be carefully monitored for a relapse.

Genotype analysis and phenotypic manifestations of children with intermediate sweat chloride test results.

STUDY OBJECTIVES: Cystic fibrosis (CF) is one of the most common inherited diseases among whites. Since the cloning of the CF transmembrane conductance regulator (CFTR) gene, a number of studies have focused on associations between the genotype and phenotype in CF. This had led to the progressive identification of new groups of patients, including those who have mild lung disease and those who have normal sweat chloride values (< 60 mEq/L). The aim of the present work was to provide information on the genotype and the phenotypic characteristics of children with intermediate-range sweat chloride test results. PATIENTS AND RESULTS: We focused on children referred to the pulmonary department for various types of pulmonary disease and who had several sweat chloride test results with median values in the range of 40 to 60 mEq/L. Twenty-four patients over a 10-year period were enrolled (mean age, 4.8 years). Respiratory manifestations at initial evaluation included recurrent bronchitis, wheezing, chronic cough, and pneumonia. The duration of the follow-up ranged from 0.5 to 10.5 years. Sputum cultures revealed the presence of Haemophilus influenzae (10 children), Staphylococcus aureus (4 children), and Pseudomonas aeruginosa (3 children). Pancreatic insufficiency was found in two patients. Analysis of the entire coding sequence allowed identification of 16 known mutations in CFTR gene. Fifteen chromosomes (31.2%) carried a mutation in CFTR gene and one allele carried two mutations. Three patients were homozygous or double heterozygous (DeltaF508/DeltaF508, DeltaF508/3849 + 10 kb C-->T, S1235R/G551D). The 5-thymidine allele was identified in four children. CONCLUSION: These results indicate an higher frequency of CFTR gene mutations in patients with borderline sweat chloride test results, compared to data reported in the general population. They lead to the recommendations for complete pulmonary and GI investigations in this group of patients, as well as assiduous care and medical follow-up.

Distinct sputum cytokine profiles in cystic fibrosis and other chronic inflammatory airway disease.

The dominant role of inflammation in airways disease progression in cystic fibrosis (CF) is now well established and, based on recent findings, the possibility of an inappropriate inflammatory response in the lung of patients with CF has emerged. In order to characterize this response, the aim of the present work was to evaluate the levels of a number of pro- and anti-inflammatory cytokines in the sputum of CF children and to compare these levels to those observed in the sputum from non-CF children with diffuse bronchiectasis (DB). Three groups of patients were investigated: a group of 25 CF children (mean age: 12.2 yrs), a group of 10 non-CF children with DB (mean age 11.5 yrs), and a group of five healthy young adults (mean age 24 yrs). Elevated concentrations of pro-inflammatory cytokines, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-8 were found in children with CF and in non-CF children with DB, with significantly higher concentrations of IL-1beta in CF children. Analysis of the natural anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) and type II TNF soluble receptor (sTNFRII) concentrations showed distinct patterns, with elevated levels of both inhibitors in CF patients, whereas only sTNFRII was found to be increased in non-CF children with DB. IL-10 data indicated low concentrations in the CF group. In all CF children, the concentrations of IL-6 in the airways were extremely low, independent of the clinical, bacteriological or functional status. By contrast, significantly increased IL-6 levels were found in non-CF children with DB. These results document distinct cytokine profiles in cystic fibrosis patients and noncystic fibrosis patients. They also suggest that impairment of interleukin-6 expression may represent an important component of the excessive inflammatory response observed in cystic fibrosis.

[Clinical and respiratory function follow-up of 39 infants treated with neonatal respiratory extracorporeal assistance]. / Suivi clinique et fonctionnel respiratoire de 39 nourrissons traités par assistance respiratoire extracorporelle néonatale.

UNLABELLED: The aim of this prospective study was to evaluate the consequences of neonatal treatment with a venovenous extracorporeal respiratory assistance. POPULATION AND METHODS: Thirty nine neonates (28 boys) with acute respiratory failure were included. Extracorporeal respiratory assistance consisted of an apnoeic oxygenation with low frequency positive pressure ventilation and extracorporeal membrane CO2 removal through a venous single canula perfusion circuit. The causes of respiratory distress were: 15 meconium aspiration syndrome, 12 respiratory distress syndrome, six hyaline membrane disease, three sepsis, two diaphragmatic hernia, and one post-surgery Mendelson syndrome. The mean duration of mechanical ventilation was 18 days, including 5 days of extracorporeal respiratory assistance. The prospective follow-up included physical examination, chest radiographs, scintigraphy and pulmonary function tests. These tests studied the following parameters: functional residual capacity by helium dilution technique, lung resistance and dynamic lung compliance by the esophageal balloon technique and blood gases with arterialized blood samples. RESULTS: The mean duration of the follow-up was 21.3 months (6 months to 5 years). Results showed in the first year 33% of children with chronic obstructive pulmonary disease and chest (X-ray abnormalities, such as bronchopulmonary dysplasia in 23% of children. Data of pulmonary function test at the end of the first year: lung resistance and functional residual capacity were within limits of predicted values for height, and dynamic lung compliance was slightly decreased; according to the analysis of the functional profile: 31% without abnormality, 41% of obstructive syndrome and 26% with restrictive pattern. Blood gases were normal in 37 children. At the end of the second year, we noticed normal functional residual capacity, an increase of lung resistance while lung compliance was normalized; functional profile was quite different: with a decrease of the number of patients without abnormality (22%) and increase of those with obstructive syndrome (56%). CONCLUSION: The percentage of abnormalities is high but these are moderate in most cases, especially if we compare with the initial seriousness of the pulmonary pathology. We suggest a regular follow-up to study the respective incidence of pulmonary disease and/or extracorporeal respiratory assistance over these abnormalities.

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.

Chest physiotherapy in cystic fibrosis: improved tolerance with nasal pressure support ventilation.

OBJECTIVE: Chest physiotherapy (CPT) is an integral part of the treatment of patients with cystic fibrosis (CF). CPT imposes additional respiratory work that may carry a risk of respiratory muscle fatigue. Inspiratory pressure support ventilation (PSV) is a new mode of ventilatory assistance designed to maintain a constant preset positive airway pressure during spontaneous inspiration with the goal of decreasing the patient's inspiratory work. The aim of our study was 1) to evaluate respiratory muscle fatigue and oxygen desaturation during CPT and 2) to determine whether noninvasive PSV can relieve these potential adverse effects of CPT. METHODS: Sixteen CF patients in stable condition with a mean age of 13 +/- 4 years participated to the study. For CPT, we used the forced expiratory technique (FET), which consisted of one or more slow active expirations starting near the total lung capacity (TLC) and ending near the residual volume. After each expiration, the child was asked to perform a slow, nonmaximal, diaphragmatic inspiration. After one to four forced breathing cycles, the child was asked to cough and to expectorate. A typical 20-minute CPT session consisted of 10 to 15 FET maneuvers separated by rest periods of 10 to 20 breathing cycles each. During the study, each patient received two CPT sessions in random order on two different days, at the same time of day, with the same physiotherapist. During one of these two sessions, PSV was provided throughout the session (PSV session) via a nasal mask using the pressure support generator ARM25 designed for acute patients (TAEMA, Antony, France). The control session was performed with no nasal mask or PSV. Both CPT sessions were performed without supplemental oxygen. Lung function and maximal inspiratory pressures (PImax) and expiratory pressures (PEmax) were recorded before and after each CPT session. RESULTS: Mean lung function parameters were comparable before the PSV and the control sessions. Baseline pulse oximetry (SpO2) was significantly correlated with the baseline vital capacity (% predicted) and forced expiratory volume in 1 second (FEV1) (% predicted). PSV was associated with an increase in tidal volume (Vt) from 0.42 +/- 0.01 liters to 1.0 +/- 0.02 liters. Respiratory rate was significantly lower during PSV. SpO2 between the FET maneuvers was significantly higher during PSV as compared with the control session. SpO2 decreases after FET were significantly larger during the control session (nadir: 91.8 +/- 0. 7%) than during the PSV session (93.8 +/- 0.6%). Maximal pressures decreased during the control session (from 71.9 +/- 6.1 to 60.9 +/- 5.3 cmH2O, and from 85.3 +/- 7.9 to 77.5 +/- 4.8 cmH2O, for PImax and PEmax, respectively) and increased during the PSV session (from 71.6 +/- 8.6 to 83.9 +/- 8.7 cmH2O, and from 80.4 +/- 7.8 to 88.0 +/- 7.4 cmH2O, for PImax and PEmax, respectively). The decrease in PEmax was significantly correlated with the severity of bronchial obstruction as evaluated based on baseline FEV1 (% predicted). Forced expiratory flows did not change after either CPT session. The amount of sputum expectorated was similar for the two CPT sessions (5.3 +/- 5.3 g vs 4.6 +/- 4.8 g after the control and PSV session, respectively; NS). Fifteen patients felt less tired after the PSV session. Ten patients reported that expectoration was easier with PSV, whereas 4 did not note any difference; 2 patients did not expectorate. Nine patients expressed a marked and 5 a small preference for PSV, and 2 patients had no preference. The physiotherapists found it easier to perform CPT with PSV in 14 patients and did not perceive any difference in 2 patients. DISCUSSION: Our study in CF children shows that respiratory muscle performance, as evaluated based on various parameters, decreased after CPT and that significant falls in oxygen saturation occurred after the FET maneuvers despite the quiet breathing periods between each FET cycle. These unwanted effects of CPT were

Chronic interstitial lung disease in children: response to high-dose intravenous methylprednisolone pulses.

The prognosis for children with chronic interstitial lung disease is poor and the mortality rate is high, especially in infants. This explains the many therapeutical protocols which have been proposed and investigated by several authors. In the present work, we evaluated the response of three infants with idiopathic pulmonary fibrosis to high-dose intravenous prednisolone pulses. The patients were referred to the department at the age of 4, 17, and 3 months, respectively. The diagnosis was confirmed by open lung biopsy and intravenous pulse methyl prednisolone therapy was started with the following protocol: 300 mg/m2 methylprednisolone daily for 3 days, repeated every 4 to 6 weeks. Because of the extreme severity of the respiratory distress at the time of diagnosis, the intravenous pulse treatments were initially complemented by oral prednisone. Clinical improvement was noticed within 6 months with progressive correction of hypoxemia. After follow-up for 3.5 to 4 years, with a total number of pulses of 37, 26, and 32, respectively, the children are symptom-free and do not require oxygen supplementation. During this period, no side effects and no adrenal insufficiency could be documented. Based on current knowledge of steroid action, it can be speculated that the response to intermittent high-dose intravenous methylprednisolone may explain the ability of this mode of hormone administration to maintain an adequate level of glucocorticoid receptor expression. More information and trials through multicenter collaborations are needed to assess therapeutical protocols of repeated high-dose intravenous steroid treatment.

Expression of insulin-like growth factors and their binding proteins by bronchoalveolar cells from children with and without interstitial lung disease.

The involvement of the insulin-like growth factor (IGF) system in lung growth and repair following injury is sustained by a number of studies. Based on this knowledge, the aim of the present work was to document the expression of the IGFs and their binding proteins by alveolar cells obtained by bronchoalveolar lavage (BAL). Two groups were investigated: a control group of five children and a group of 11 children referred to the department for exploration of interstitial lung disease (ILD). Components of the IGF system studied included IGF-I, IGF-II and IGF-binding proteins (IGFBP). Expression of these factors was analysed at the level of messenger ribonucleic acid (mRNA) (by semi-quantitative reverse transcription polymerase chain reaction techniques), and of protein for the IGFBPs. In addition, expression of two major cytokines associated with the inflammatory process, tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), was also documented. In children without parenchymal disease, the growth factor expressed was IGF-I, in association with the presence of mRNA for IGFBP-2 in all cases. In children with ILD, expression of IGF-I was observed in nine patients and of IGF-II in three patients, and the presence of IGFBP-2 was found in all extracts analysed (mRNA and proteins). Evaluation of IGFBP-2 expression indicated an increase in the group of children with ILD. Interestingly, a significant association was observed between the increase in IGFBP-2 expression and TGF-beta expression. The present data emphasize the presence on insulin-like growth factor-binding protein-2 in the BAL of all patients, and suggest that this protein may be an important factor of the injury/repair processes during the progression of alveolar inflammation.

Impaired ability of Cftr knockout mice to control lung infection with Pseudomonas aeruginosa.

The present study was aimed at investigating the innate susceptibility of C57BL/6-Cftrunc/Cftrunc knockout [B6-Cftr (-/-)] mice to pulmonary infection with Pseudomonas aeruginosa. Our results indicate that 58.4% of B6-Cftr (-/-) mice died within 6 d following lung infection with 10(5) P. aeruginosa entrapped in agar beads, whereas only 12.1% of B6-Cftr (+/+) mice died over the same period of time. Moreover, the number of bacteria recovered from the lungs of B6-Cftr (-/-) mice 3 and 6 d after infection was significantly higher than that observed in their littermate controls. No correlation was found between the weight or age of the animals and the number of viable bacteria recovered from the lungs of mice. Histopathological examination of lung sections from P. aeruginosa-infected mice revealed that the infection results in a severe bronchopneumonia. Both B6-Cftr (-/-) knockout mice and their littermate controls developed similar lung pathology during the course of infection. Overall, results reported in the present study suggest that a defect at the Cftr locus leads to an exacerbation of P. aeruginosa lung infection resulting in a dramatically increased mortality rate and higher bacterial load.

[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.