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.

[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.

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.

Activation of MAP kinase (ERK1/2) in human neonatal colonic enteric nervous system.

The aim of this study was to examine mitogen-activated protein kinase (ERK1/2) activation in the human neonatal colonic enteric nervous system. For this, we investigated by immunocytochemistry the cellular localization of phosphorylated ERK1/2 (P-ERK) in a series of normal human colon samples removed from newborns and in patients with intestinal obstruction such as Hirschsprung's disease (HSCR), stenosis and atresia. We checked the presence of P-ERK in the three distinct histological layers of normal colon. Phosphorylated ERK was detected in the colonic mucosa, in the enteric nervous system and in endothelial cells. In the mucosa from normal colon, P-ERK was detected at the upper part of the crypt, while P-ERK activation in epithelial cells is altered in HSCR, stenosis and atresia. In the normal colon, strong P-ERK staining was detected in myenteric and submucosal enteric plexuses. Using confocal microscopy analyses, we observed that P-ERK staining was localized in enteric glial cells and not in enteric neurons. Strong P-ERK staining was also observed in plexuses from stenosis and atresia whereas in HSCR, hypertrophic nerve fibres were not stained.

[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.

Effect of inspiratory threshold loading on ventilatory kinetics during constant-load exercise.

Humoral factors play an important role in the control of exercise hyperpnea. The role of neuromechanical ventilatory factors, however, is still being investigated. We tested the hypothesis that the afferents of the thoracopulmonary system, and consequently of the neuromechanical ventilatory loop, have an influence on the kinetics of oxygen consumption (VO2), carbon dioxide output (VCO2), and ventilation (VE) during moderate intensity exercise. We did this by comparing the ventilatory time constants (tau) of exercise with and without an inspiratory load. Fourteen healthy, trained men (age 22.6 +/- 3.2 yr) performed a continuous incremental cycle exercise test to determine maximal oxygen uptake (VO2max = 55.2 +/- 5.8 ml x min(-1) x kg(-1)). On another day, after unloaded warm-up they performed randomized constant-load tests at 40% of their VO2max for 8 min, one with and the other without an inspiratory threshold load of 15 cmH2O. Ventilatory variables were obtained breath by breath. Phase 2 ventilatory kinetics (VO2, VCO2, and VE) could be described in all cases by a monoexponential function. The bootstrap method revealed small coefficients of variation for the model parameters, indicating an accurate determination for all parameters. Paired Student's t-tests showed that the addition of the inspiratory resistance significantly increased the tau during phase 2 of VO2 (43.1 +/- 8.6 vs. 60.9 +/- 14.1 s; P < 0.001), VCO2 (60.3 +/- 17.6 vs. 84.5 +/- 18.1 s; P < 0.001) and VE (59.4 +/- 16.1 vs. 85.9 +/- 17.1 s; P < 0.001). The average rise in tau was 41.3% for VO2, 40.1% for VCO2, and 44.6% for VE. The tau changes indicated that neuromechanical ventilatory factors play a role in the ventilatory response to moderate exercise.

[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.

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 effects of prior cycling and a successive run on respiratory muscle performance in triathletes.

The aim of the present study was to compare the effects of prior cycling and a successive run on respiratory muscle performance during a cycle-run succession as performed in the triathlon. We hypothesized that despite the moderate intensity of exercise and the absence of exhaustion, the crouched cycling position would induce a decrease in respiratory muscle performance that would be reversed by the successive vertical run position. Ten male triathletes (22.6 +/- 1.1 yr) performed a four-trial protocol: (1) an incremental cycle test to assess maximal oxygen uptake (VO2max), (2) 20 min of cycling (C), (3) 20 min of running (R), and (4) 20 min of cycling followed by 20 min of running (C-R). Trials 2, 3 and 4 were performed at the same metabolic intensity, i. e., 75 % of VO2max. Respiratory muscle force was assessed by measuring maximal expiratory (P(Emax)) and inspiratory (P(Imax)) pressures from the functional residual capacity (FRC) before and 10 min after C, R, and C-R. Respiratory muscle endurance was assessed one day before and 30 min after C, R, and C-R, by measuring the time limit (T(lim)), which corresponds to the length of time a respiratory load can be sustained before the process of fatigue develops sufficiently to cause task failure. The results showed a similar significant decrease in P(Imax) (132.4 +/- 4.9 versus 125.7 +/- 5.6 cm H2O, p < 0.05) and T(lim) (5.22 +/- 0.28 versus 3.68 +/- 0.32 min, p < 0.05) post-C and post-C-R (133.7 +/- 4.0 versus 126.9 +/- 5.2 cm H2O, and 5.29 +/- 0.18 versus 3.49 +/- 0.41 min, respectively, p < 0.05) compared with the pre-trial values. In contrast, P(Imax) and T(lim) were not significantly decreased post-R (131.8 +/- 6.1 cm H2O versus 129.6 +/- 6.4 cm H2O, and 4.90 +/- 0.69 versus 4.40 +/- 0.56 min, respectively, p > 0.05). We concluded that moderate intensity exercise not performed to exhaustion induced a decrease in respiratory muscle performance. Moreover, the respiratory muscle fatigue induced by prior cycling was maintained, and neither reversed nor worsened, by the successive run.

[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.

The effect of cycling followed by running on respiratory muscle performance in elite and competition triathletes.

This study investigated the possibility of there being differences in respiratory muscle strength and endurance in elite and competition triathletes who have similar maximal oxygen uptakes (VO(2max)) and ventilatory thresholds (Th(vent)). Five internationally-ranked elite, [mean (SD) age 23.8 (1.4) years] and six nationally- and regionally-ranked competition [age 21.1 (1.1) years] male triathletes performed two successive trials: first an incremental cycle test to assess VO(2max) and Th(vent) and second 20 min of cycling followed by 20 min of running (C-R) at intensities higher than 85% VO(2max). Cardioventilatory data were collected every minute during the two trials, using an automated breath-by-breath system. Maximal expiratory and inspiratory (P(Imax)) strength were assessed before and 10 min after C-R from the functional residual capacity. Respiratory muscle endurance was assessed 1 day before and 30 min after C-R by measuring the time limit (t(lim)). The results showed firstly that during C-R, the competition triathletes had significantly (P < 0.05) higher minute ventilation [mean (SEM) 107.4 (3.1) compared to 99.8 (3.7) l x min(-1)], breathing frequency [44.4 (2.0) compared to 40.2 (3.4) x min(-1)] and heart rate [166 (3) compared to 159 (4) beats x min(-1)] and secondly that after C-R, they had significantly lower P(Imax) [127.1 (4.2) compared to 130.7 (3.0) cmH(2)O] and t(lim) [2:35 (0:29) compared to 4:12 (0:20) min] than the elite triathletes. We conclude that, despite similar VO(2max) and Th(vent), the competition triathletes showed less extensive adaptive mechanisms, including those in the respiratory muscles, than did the elite triathletes. This led to higher ventilation, which appeared to be the cause of the faster development of fatigue in the inspiratory muscles in this group.

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.

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.