Does training respiratory physicians in clinical respiratory physiology and interpretation of pulmonary function tests improve core knowledge?

Lung function tests have a major role in respiratory medicine. Training in lung function tests is variable within the European Union. In this study, we have shown that an internship in a lung function tests laboratory significantly improved the technical and diagnostic skills of French respiratory trainees.

[Pulmonary function test: The testing of children]. / Exploration fonctionnelle respiratoire : explorer l'enfant.

In paediatrics, the pulmonary function test (PFT) is most often performed to support the diagnosis or in follow-up of asthma patients. Whatever the pathology responsible for respiratory symptoms and/or functional impairment, repeated PFTs make it possible to establish a prognosis (pulmonary function trajectories…) and to orient preventive interventions. PFT can be performed routinely from the age of three years, provided that the following requirements are met: suitable techniques and equipment, staff trained to apply the techniques and to receive young children, reference values for each technique indicating the limits of normal values and of between-test significant variation. From the age of three, children can be subjected to tidal breathing measurement of: resistance of the respiratory system (oscillometry, Rrs; airflow interruption, Rint) or of airways specific resistance (sRaw) and functional residual capacity (by applying a dilution technique). With maturity, the child will become capable of mobilizing his or her slow vital capacity to measure total lung capacity (TLC), once again by applying a dilution technique, then later by breathing against a closed shutter (plethysmography TLC and Raw). Finally, the child will be able to carry out forced expiration (forced spirometry) along with all of the other PFTs. It is important to take into account the paediatric adaptations specified in the international recommendations regarding the performance, reproducibility and quality of PFTs targeting this population.

[Respiratory function testing in infants: recommendations on normal values]. / EFR du nourrisson: le point sur les valeurs normales.

The present document is being produced on behalf of the French Society of the Physiology Task Force on standards for Infant Respiratory Function Testing whose aim is to provide guidelines for good laboratory practices according to the latest international recommendations. Application of such recommendations could be of particular value when attempting to develop standardized protocols in the scope of multi-centre trials. The first part resume these recommendations about apparatus, acquisition system and software for Infant Respiratory Function Testing. The second part focuses on physiological principles and practical considerations: calibration procedure, infant conditioning, tidal breathing measurements, and occlusion techniques for assessing passive respiratory mechanics, plethysmographic measurements of lung volume and airway resistance and forced expiratory flows measurements. The major problem when collecting lung function data is that of predicted values. Valid reference data, set up according to these recommendations, are, to date, still to be established. The last part of the document provides a review of the literature concerning infant respiratory function reference data and a resume of the most used of them. This document will clearly need to be updated regularly in response to advances in knowledge in this field.

[Cystic fibrosis: how to use pulmonary function tests]. / Mucoviscidose: du bon usage des explorations fonctionnelles respiratoires.

INTRODUCTION: Neonatal screening for cystic fibrosis (CF) leads to early dedicated specialist care for all patients. BACKGROUND: Pulmonary function tests (PFT) are mandatory for routine monitoring of CF patients. The aim of this article is to review the current guidelines for PFTs in CF, particularly the type of test, the age and the clinical status of the patient. VIEWPOINT: The regular use of spirometry is generally accepted. Many other tests are used but their clinical value in the routine follow-up of CF patients remains to be established. CONCLUSION: Further efforts should be made to evaluate the value of PFTs in CF, particularly in very young children.

[Early lung disease in infants with cystic fibrosis. Diagnostic tools and possible therapeutic pathways]. / Atteinte respiratoire précoce chez les nourrissons atteints de mucoviscidose. Outils de diagnostic et pistes pour la prise en charge.

The lungs of infants with cystic fibrosis (CF) have been considered to be normal at birth. However, recent data indicates that this is unlikely to be true in most cases. Animal CF-models developed in the early 2000s have shown that constitutional airway narrowing may be present at birth, and is associated with both functional and structural abnormalities. Longitudinal birth cohort studies have shown that 25 % of CF infants followed in specialized centers, while being asymptomatic, showed decreased lung function at 3months of age. Air trapping was present in 68 % and bronchiectasis in 28 % of patients at the same age. The presence of neutrophil elastase in the bronchoalveolar lavage at 3months of age tripled the risk of bronchiectasis at the age of 3years. Currently available tools such as infant pulmonary function tests (both the jacket and multiple breath washout) as well as high-resolution volume controlled chest-computed tomography or functional magnetic resonance imaging will facilitate early intervention trials in the very near future. The role of such tools for the routine follow-up of patients, and the ability of early therapeutic interventions to alter the natural history of CF-lung disease should soon be established.

Correlation between cardio-pulmonary exercise test variables and health-related quality of life among children with congenital heart diseases.

BACKGROUND: Health-related quality of life (HR-QoL) stands as a determinant "patient-related outcome" and correlates with cardio-pulmonary exercise test (CPET) in adults with chronic heart failure or with a congenital heart disease (CHD). No such correlation has been established in pediatric cardiology. METHODS AND RESULTS: 202 CHD children aged 8 to 18 performed a CPET (treadmill n=96, cycle-ergometer n=106). CHD severity was stratified into 4 groups. All children and parents filled out the Kidscreen HR-QoL questionnaire. Peak VO2, anaerobic threshold (AT), and oxygen pulse followed a downward significant trend with increasing CHD severity and conversely for VE/VCO2 slope. Self-reported and parent-reported physical well-being HR-QoL scores correlated with peak VO2 (respectively r=0.27, p<0.0001 and r=0.43, p<0.0001), percentage of predicted peak VO2 (r=0.28, p=0.0001 and r=0.41, p<0.0001), and percentage of predicted VO2 at AT (r=0.22, p<0.01 and r=0.31, p<0.0001). Significant correlations were also observed between several HR-QoL dimensions and dead space to tidal volume ratio (VD/VT), oxygen uptake efficiency slope (OUES), oxygen pulse but never with VE/VCO2 slope. The strongest correlations were observed in the treadmill group, especially between peak VO2 and physical well-being for parents (r=0.57, p<0.0001) and self (r=0.40, p<0.0001) reported HR-QoL. CONCLUSIONS: Peak VO2 and AT are the two CPET variables that best correlated with HR-QoL in this large pediatric cohort, parents' reports being more accurate. If HR-QoL is involved as a "PRO" in a pediatric cardiology clinical trial, we suggest using parents related physical well-being HR-QoL scores. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (number NCT01202916).

[Consequences of mechanical ventilation on diaphragmatic function]. / Conséquences de la ventilation mécanique sur le diaphragme.

INTRODUCTION: Mechanical ventilation is associated with ventilator-induced diaphragmatic dysfunction (VIDD) in animal models and also in humans. BACKGROUND: The main pathophysiological pathways implicated in VIDD seems to be related to muscle inactivity but may also be the consequence of high tidal volumes. Systemic insults from side effects of medication, infection, malnutrition and hypoperfusion also play a part. The diaphragm is caught in the cross-fire of ventilation-induced and systemic-induced dysfunctions. Intracellular consequences of VIDD include oxidative stress, proteolysis, impaired protein synthesis, autophagy activation and excitation-contraction decoupling. VIDD can be diagnosed at the bedside using non-invasive magnetic stimulation of the phrenic nerves which is the gold standard. Other techniques involve patient's participation such as respiratory function tests or ultrasound examination. CONCLUSION AND PERSPECTIVES: At this date, only spontaneous ventilatory cycles and perhaps phrenic nerve stimulation appear to diminish the severity of VIDD in humans but several pathways are currently being examined using animal models. Specific pharmacological options are currently under investigation in animal models.

A standardized method for the evaluation of respiratory muscle endurance in patients with Duchenne muscular dystrophy.

The aim of the study was to develop a standardized method using controlled breathing to quantify respiratory muscle endurance in children with Duchenne muscular dystrophy (DMD) and to test its reproducibility. In 10 DMD patients, all between 10 and 14 years (mean age, 11.5 +/- 1.5 years), except for two patients of 20 and 22 years, and 10 healthy children (mean age, 12 +/- 1 years), we measured the maximal time (Tlim) that a threshold load fixed at 35% of the individual maximal inspiratory pressure (Pimax) could be tolerated. We asked the children to maintain their rest breathing pattern until exhaustion using visual feedback and an auditory signal. The mean Tlim in the DMD children was 4.45 +/- 1.45 min and values were reproducible. All healthy children were able to obtain Tlim values greater than 30 min. The respiratory muscles of DMD children are more susceptible to fatigue than those of healthy subjects. This method should be satisfactory for estimating the effect of treatment and for the specific training of respiratory muscles in DMD patients without significant learning disability.

Effect of food restriction on lactate sarcolemmal transport.

The objective of this study was to investigate the effects of 6 weeks of food restriction (FR) on sarcolemmal lactate transport in rats. The daily food consumption of rats was monitored for 10 days, after which they were assigned to either a control group (CTL, n = 7) that consumed food ad libitum or an FR group (n = 7) that received a daily ration equal to 60% of their predetermined baseline food intake. After the 6-week period, we observed in red gastrocnemius (RG) a fall of 48% in glycogen content (P <.01) and a reduction in glutathione peroxidase activity (P <.05), confirming that the FR program was well executed. FR resulted in a reduction in muscle lactate (P <.05) and liver glycogen contents (P <.01). Moreover, hyperlactatemia was noted in the FR group: 1.77 +/- 0.24 versus 2.67 +/- 0.29 mmol/L (P <.05). Lactate transport capacity was significantly increased (P <.05) in FR rats, although monocarboxylate transporter isoforms (MCT1 and MCT4) did not change significantly. We conclude that FR alters sarcolemmal lactate transport activity without affecting MCT1 and MCT4 expression.

The effect of exercise modality on respiratory muscle performance in triathletes.

PURPOSE: The aim of this study was to examine the effects of the cycle-run and run-cycle successions of the triathlon and duathlon, respectively, on respiratory muscle strength and endurance. METHODS: Respiratory muscle strength was assessed by measuring maximal inspiratory (P(Imax)) and expiratory (P(Emax)) pressures. Respiratory muscle endurance was assessed by measuring the time limit (T(lim)). Twelve triathletes participated in a three-trial protocol. The first trial consisted of an incremental cycle test to assess the maximal oxygen uptake (.VO(2max)) of triathletes. Trial 2 consisted of 20 min of cycling followed by 20 min of running (C-R), and trial 3 consisted of 20 min of running followed by 20 min of cycling (R-C). Trials 2 and 3 were performed at the same metabolic intensity (%.VO(2max)). P(Imax) and P(Emax) were measured before and 10 min after C-R and R-C, and 1 min after the post-C-R and post-R-C T(lim) measurements (P(Imax) 1'). T(lim) was measured 1 d before and 30 min after C-R and R-C. RESULTS: The results showed a significant decrease in P(Imax) after C-R (126.7 +/- 4.3 cmH(2)O, P < 0.05) and R-C (123.7 +/- 4.9 cmH(2)O, P < 0.05) compared with the baseline values (130 +/- 3.8 and 129.6 +/- 4.3 cmH(2)O, respectively). P(Imax) 1' showed a significantly greater decrease after R-C versus C-R (111.2 +/- 5.5 cmH(2)O vs 121.2 +/- 3.9 cmH(2O), respectively, P < 0.001). Tlim after C-R (3.3 +/- 0.3 min) and R-C (2.1 +/- 0.3 min) decreased significantly compared with baseline values (4.19 +/- 0.3 min and 4.02 +/- 0.3 min, respectively). However, the Tlim decrease after R-C was significantly greater than after C-R (P < 0.001). CONCLUSION: We concluded that respiratory muscle strength and endurance were less decreased after the cycle-run succession and that cycling induced a greater decrease in respiratory muscle endurance than running.

Effects of erythropoietin administration in training athletes and possible indirect detection in doping control.

PURPOSE: This study investigated the effects of repeated subcutaneous injection of rHuEpo (50 IU x kg(-1)) in athletes and proposes a method based on the measurement in blood samples of the sTfR/serum protein ratio to determine if the observed values of this marker are related to rHuEpo abuse. METHODS: Serum erythropoietin concentrations, and hematological and biochemical parameters were evaluated, during treatment and for 25 d posttreatment in nine training athletes. Moreover, the effect of rHuEpo administrations on the maximum oxygen uptake (VO2max) and ventilatory threshold (VT) of these athletes was also studied. Threshold values for sTfr and the sTfr/serum protein ratio were determined from 233 subjects (185 athletes, 15 athletes training at moderately high altitude, and 33 subjects living at >3000 m). RESULTS: Significant changes in reticulocytes, hemoglobin (Hb) concentration, hematocrit (Hct), sTfr, and sTfr/serum proteins were observed during and after rHuEpo treatment. The maximal heart rate of 177 beats x min(-1) at the beginning of the study was significantly higher than the value of 168 beats x min(-1) after 26 d of rHuEpo administration. Compared with the values measured at baseline, the VT measured after rHuEpo administration occurred at a statistically significant high level of oxygen uptake. CONCLUSIONS: When oxygen uptake measured at the VT was expressed as a percentage of V02 max, the values obtained were also significantly higher. The increased values of Tfr and sTfr/serum proteins, respectively, above 10 microg x mL(-1) and 153, indicated the probable intake of rHuEpo.

[Maximal respiratory pressures in children: the methodological challenge]. / Pressions respiratoires maximales chez l'enfant: les exigences méthodologiques.

INTRODUCTION: Measurement of maximal respiratory pressures against an occlusion has been used for a long time to assess respiratory muscle strength in the follow up of children with respiratory disease. In the early stage of disease this is the main test for diagnosing respiratory muscle involvement and the degree of that involvement. STATE OF KNOWLEDGES: The interpretation of the results is difficult on account of variability of the measurements and of the reference values. The aim of this article is to present, in the form of a literature review, the normal values available and the different determining factors as well as the advantages and limitations of these measurements. PERSPECTIVES: The use by all the centres undertaking maximal respiratory pressure measurements in children of methodological techniques similar to those presented in this revue could be the starting point for obtaining an identical range of reference values for all. CONCLUSION: Age, sex and the level of physical aptitude seem to be the most important determinants of maximal respiratory pressures. However, other methodological factors such as co-operation, training of the child in the performance of the manoeuvres and the type of device and protocol used, will all influence the results. These factors must be taken into consideration in order to diminish, as much as possible, the variability of the maximal pressures obtained.

[Indications and application of exercise tests in children]. / Indications et réalisation pratique des épreuves d'exercice chez l'enfant.

Exercise tests are routinely used in children to assess cardio-respiratory and muscular adaptations to exercise. However these tests are of relatively recent use, and there is a lack of standardization and of relevant data in large groups in this population. The aim of this paper was to specify the common medical indications of exercise tests in children, to propose standardized protocols of these tests in some of the most common pathological situations as: exercise-induced asthma, chronic respiratory diseases (bronchopulmonary dysplasia, cystic fibrosis), muscular diseases. These tests can provide clinically relevant parameters only when they are used in strict conditions of standardization.

[Ventilatory response to maximal exercise in healthy children]. / La réponse ventilatoire à l'exercice maximal chez l'enfant sain.

INTRODUCTION: The evaluation of the ventilatory response of children during exercise is essential to determine its role in impaired exercise tolerance. The aim of this review is to describe the variables and the values of maximal ventilatory parameters observed in healthy children in the published literature. STATE OF ART: The maximal ventilation (VEmax) and the tidal volume (VTmax) increase in a linear fashion with age and plateau in boys at 15 years, and in girls at 13 years. The main variables for the parameters connected to volume--VEmax and VTmax--are anthropometric characteristics, in particular, the lean body mass. Most studies show a value of 30 ml.kg(-1) for a VTmax on the total body mass in pre-puberty and a slight increase thereafter. The ventilatory reserves and the VTmax on vital capacity increase with age until respective values of 30% and 50% are reached at 17 years. The maximal parameters connected to time are independent of anthropometric characteristics. The TI/TTOT ratio (inspiratory time to total time of the respiratory cycle) is stable with a value of 0.5. The maximal respiratory frequency decreases slightly with age without differences between the genders. PERSPECTIVES AND CONCLUSION: Only studies of larger numbers of children, proposing relationships derived from allometric equations, will be able to provide real reference values.

[Maximal oxygen uptake in healthy children: factors of variation and available standards]. / La consommation maximale d'oxygène chez l'enfant sain: facteurs de variation et normes disponibles.

Aerobic physical fitness, in children, is assessed by measurement of the maximal oxygen consumption during exercise testing. Representative norms of the studied population are required for interpretation. The aim of this article is to specify and review the available VO2max norms and factors of variation, including: sex, anthropometric characteristics (height, lean body mass and weight) and physical activity level. Ideally, VO2max norms should include lean body mass and physical activity with an allometric equation. Since such norms do not exist today, interpretation remains difficult. In France, the must satisfactory norms for non trained children include body mass without an allometric equation (boys: 47 +/- 2 ml.mn.-1 kg-1, girls: 40 +/- 3 ml.mn.-1 kg-1 with a post puberty decrease). Further studies on VO2max norms that include lean body mass and a physical activity questionnaire are required to improve exercise test interpretation in children.

Targeting neonatal ischemic brain injury with a pentapeptide-based irreversible caspase inhibitor.

Brain protection of the newborn remains a challenging priority and represents a totally unmet medical need. Pharmacological inhibition of caspases appears as a promising strategy for neuroprotection. In a translational perspective, we have developed a pentapeptide-based group II caspase inhibitor, TRP601/ORPHA133563, which reaches the brain, and inhibits caspases activation, mitochondrial release of cytochrome c, and apoptosis in vivo. Single administration of TRP601 protects newborn rodent brain against excitotoxicity, hypoxia-ischemia, and perinatal arterial stroke with a 6-h therapeutic time window, and has no adverse effects on physiological parameters. Safety pharmacology investigations, and toxicology studies in rodent and canine neonates, suggest that TRP601 is a lead compound for further drug development to treat ischemic brain damage in human newborns.