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).

Interrupter resistance to measure dose-response to salbutamol in wheezy preschool children.

AIM: Using a non-invasive lung function technique (interrupter resistance, Rint), we aimed to determine whether a dose-response to salbutamol could be detected in wheezy preschool children and if so, which dose of salbutamol should be administered to routinely evaluate bronchial reversibility. METHOD: Wheezy children (3 to <7 years) were enrolled in a prospective multicenter study. Rint was measured at baseline, and after random assignment to a first dose (100 or 200 µg) and a second dose (cumulative dose: 400, 600, or 800 µg) of salbutamol. Data were analyzed using mixed modeling approach with an inhibitory maximal effect (Imax ) model, to account for a sparse sampling design. Simulations were performed to predict the percentage of children with significant Rint reversibility at several doses. RESULTS: Final results were available in 99 children out of 106 children included. The model adequately fitted the data, showing satisfactory goodness-of-fit plots and a low residual error of 8%. Children with uncontrolled symptoms had lower Imax (ie, showed less reversibility) compared to children with totally/partly controlled symptoms (0.23 vs. 0.31, P < 0.001). Dose to reach 50% of Imax (D50 ) was 51 µg. According to simulations, 88.1% of children with significant reversibility at dose 800 µg would already show significant reversibility at 400 µg. CONCLUSION: Interrupter resistance was able to measure a dose-response curve to salbutamol in wheezy preschool children, which was similar to that of older patients. Young children require a high dose of salbutamol to correctly assess airway bronchodilator response, especially these with poor symptom control.

Early cardiovascular manifestations in children and adolescents with autosomal dominant polycystic kidney disease: a single center study.

BACKGROUND: This study aims to describe the cardiovascular manifestations in children with autosomal dominant polycystic kidney disease (ADPKD) and detect their relation with kidney disease and type of gene mutation. METHODS: Twenty-one patients (7 to 19 years old) were included. Cardiovascular evaluation involved blood pressure (BP), indexed left ventricular mass (LVMI), pulse wave velocity (PWV), and carotid intima media thickness (cIMT) measurement. Patients were classified according to percentile reference values of these parameters in healthy children. The 95th percentile was the highest level of normal values. Glomerular filtration rate (GFR) and microalbuminuria were also measured. RESULTS: Antihypertensive treatment, large LVMI, high PWV, and increased cIMT were observed in 6 (28.6%), 2 (9.5%), 4 (19%), and 8 (38.1%) patients respectively. Antihypertensive treatment was not associated with either high PWV or increased cIMT. Linear correlation was noticed between LVMI and PWV (r2 = 0.243, p = 0.023) and also between LVMI and cIMT (r2 = 0.203, p = 0.041). The median age of patients with high PWV, increased cIMT, and large LVMI was 9.5, 13, and 18 years old. GFR was normal in all patients. Patients with increased cIMT presented higher levels of urine microalbumin to creatinine ratio (p = 0.025). Genetic mutation was available in 18 patients. Antihypertensive treatment was more frequent in patients without PKD1 missense mutation (p = 0.044). CONCLUSIONS: High PWV and increased cIMT indicating arterial stiffness and hypertrophic vasculopathy may be present in children with ADPKD regardless BP status, and prior to GFR decline, suggesting that vascular disease precedes chronic kidney disease in ADPKD.

Clinical and haematological risk factors for cerebral macrovasculopathy in a sickle cell disease newborn cohort: a prospective study.

Children with sickle cell disease (SCD) have a significant vascular morbidity, especially cerebral macrovasculopathy (CV), detectable by transcranial Doppler. This study aimed to identify risk factors for CV using longitudinal biological and clinical data in a SCD newborn cohort followed at the Robert Debre Reference centre (n = 375 SS/Sß(0) ). Median follow-up was 6·8 years (2677 patient-years). Among the 59 children presenting with CV, seven had a stroke. Overall, the incidence of CV was 2·20/100 patient-years [95% confidence interval (95% CI): 1·64-2·76] and the incidence of stroke was 0·26/100 patient-years (95% CI: 0·07-0·46). The cumulative risk of CV by age 14 years was 26·0% (95% CI: 20·0-33·3%). Risk factors for CV were assessed by a Cox model encompassing linear multivariate modelling of longitudinal quantitative variables. Years per upper-airway obstruction [Hazard ratio (HR) = 1·47; 95% CI: 1·05-2·06] or bronchial obstruction (HR = 1·76; 95% CI: 1·49-2·08) and reticulocyte count (HR = 1·82 per 50 × 10(9) /l increase; 95% CI: 1·10-3·01) were independent risk factors whereas fetal haemoglobin level (HR = 0·68 per 5% increase; 95% CI: 0·48-0·96) was protective. Alpha-thalassaemia was not protective in multivariate analysis (ancillary analysis n = 209). Specific treatment for upper or lower-airway obstruction and indirect targeting of fetal haemoglobin and reticulocyte count by hydroxycarbamide could potentially reduce the risk of CV.

Effect of glutamine on glucose metabolism in children with Duchenne muscular dystrophy.

BACKGROUND & AIMS: Glutamine is a potent gluconeogenic precursor and stimulates insulin secretion. Glutamine's effect on glucose metabolism in Duchenne muscular dystrophy (DMD) has never been studied. To determine plasma glucose and insulin concentrations measured during and after glutamine administration in DMD boys. We hypothesized that glutamine can modulate whole body glutamine-glucose metabolism in DMD, a genetically determined disease. METHODS: As secondary endpoints of a randomized crossover trial in 30 prepubertal DMD boys, we measured fasting blood glucose, insulin and the Homeostasis Model Assessment (HOMA) index after daily oral glutamine (0.5 g kg(-1) d(-1)) for 4 months versus placebo. In a separate time series trial in 6 prepubertal DMD boys, we measured the same endpoints as well as plasma glutamine and whole body glucose turnover (Ra,glc) (primed continuous i.v. infusion of d-[6,6-(2)D]glucose), while participants received acute oral glutamine (0.5 g kg(-1) d(-1)) continuously for 5 h. RESULTS: In the randomized trial, baseline measurements of HOMA correlated with age (r = 0,51, p = 0.007) and percent fat estimated by bioelectrical impedance analysis (BIA) (r = 0.39, p = 0.047). After 4 months glutamine supplementation, we observed no treatment or order effect on HOMA or insulin. During acute glutamine for 5 h (time series trial), plasma glutamine doubled and was associated with increased plasma insulin concentration (10.42 ± 2.54 vs 7.32 ± 1.86, p = 0.05) with no effect on plasma glucose, HOMA or Ra,glc. CONCLUSIONS: Acute glutamine transiently stimulates insulin secretion in DMD boys, which could be mediated by plasma glutamine concentrations. Fasting insulin concentration and HOMA might provide quantifiable indices of disease progression.

Impaired ventilatory and thermoregulatory responses to hypoxic stress in newborn phox2b heterozygous knock-out mice.

The Phox2b genesis necessary for the development of the autonomic nervous system, and especially, of respiratory neuronal circuits. In the present study, we examined the role of Phox2b in ventilatory and thermoregulatory responses to hypoxic stress, which are closely related in the postnatal period. Hypoxic stress was generated by strong thermal stimulus, combined or not with reduced inspired O(2). To this end, we exposed 6-day-old Phox2b(+/-) pups and their wild-type littermates (Phox2b(+/+)) to hypoxia (10% O(2)) or hypercapnia (8% CO(2)) under thermoneutral (33°C) or cold (26°C) conditions. We found that Phox2b(+/-) pups showed less normoxic ventilation (V(E)) in the cold than Phox2b(+/+) pups. Phox2b(+/-) pups also showed lower oxygen consumption (VO(2)) in the cold, reflecting reduced thermogenesis and a lower body temperature. Furthermore, while the cold depressed ventilatory responses to hypoxia and hypercapnia in both genotype groups, this effect was less pronounced in Phox2b(+/-) pups. Finally, because serotonin (5-HT) neurons are pivotal to respiratory and thermoregulatory circuits and depend on Phox2b for their differentiation, we studied 5-HT metabolism using high pressure liquid chromatography, and found that it was altered in Phox2b(+/-) pups. We conclude that Phox2b haploinsufficiency alters the ability of newborns to cope with metabolic challenges, possibly due to 5-HT signaling impairments.

Assessing change in body composition in children with Duchenne muscular dystrophy: anthropometry and bioelectrical impedance analysis versus dual-energy X-ray absorptiometry.

BACKGROUND & AIMS: To compare the ability of bioelectrical impedance analysis (BIA) and skinfold thickness (ST) measurements to estimate changes in body composition in Duchenne muscular dystrophy (DMD). METHODS: A secondary analysis was performed on 26 ambulatory DMD boys aged 3-11 y selected for a randomised trial of glutamine supplementation. We assessed fat free mass (FFM) and percentage fat mass (%FM) by BIA (monofrequency (50kHz) unit), ST measurements and a criterion method, dual-energy X-ray absorptiometry (DXA), and repeated these measures 5 mo later at 3 outpatient clinical investigation centers in France. RESULTS: When compared with DXA reference method, ST overestimated change in FFM (P<0.01), whereas BIA estimates did not differ from DXA. Concordance plots revealed that when compared with DXA, ST overestimated the increase in FFM (mean: 0.6 kg; 95% CI: 0.17 to 0.99) which led to an underestimation in %FM change (mean: -1.4%; 95% CI: -2.6 to -0.2), whereas BIA estimated change in FFM (mean: -0.05 kg; 95% CI: -0.39 to 0.29) and %FM (mean: 1.3%; 95% CI: -0.06 to 2.7) more accurately. CONCLUSIONS: BIA method can be used to follow changes in nutritional status of ambulatory DMD children or to evaluate treatment efficacy.

Lack of functional benefit with glutamine versus placebo in Duchenne muscular dystrophy: a randomized crossover trial.

BACKGROUND: Oral glutamine decreases whole body protein breakdown in Duchenne muscular dystrophy (DMD). We evaluated the functional benefit of 4 months oral glutamine in DMD. METHODOLOGY/PRINCIPAL FINDINGS: 30 ambulant DMD boys were included in this double-blind, randomized crossover trial with 2 intervention periods: glutamine (0.5 g/kg/d) and placebo, 4 months each, separated by a 1-month wash-out, at 3 outpatient clinical investigation centers in France. Functional benefit was tested by comparing glutamine versus placebo on change in walking speed at 4 months. Secondary outcome measures were: 2-minute walk test, work, power, muscle mass (urinary creatinine), markers of myofibrillar protein breakdown (urinary 3-methyl-histidine/creatinine), serum creatine phospho-kinase, body composition (fat free mass, fat mass percentage), safety and oral nutrient intake. There was no improvement in the primary end point (walking speed) or in secondary measures of muscle function (2-minute walk test, work, power) in the glutamine group compared with placebo. However, subjects receiving glutamine or placebo showed no deterioration in functional measures over the course of the 9-month trial. No differences in muscle mass, markers of protein breakdown or serum creatine phosho-kinase were observed, except for a blunted increase in fat free mass in the glutamine group which led to a greater increase in fat mass percentage. Glutamine was safe and well-tolerated. CONCLUSIONS: This trial did not identify additional benefit of 4 months oral glutamine over placebo on muscle mass or function in ambulatory DMD boys. Although apparently safe, current data cannot support routine supplementation in this population as a whole, until further research proves otherwise. TRIAL REGISTRATION: (ClinicalTrials.gov) NCT00296621.

Does exercise have deleterious consequences for the lungs of patients with chronic heart failure?

Changes in lung function in patients with chronic heart failure (CHF), usually reported at rest, may be exacerbated during exercise and induce post-exercise effects. We investigated the hypothesis that post-exercise induced changes in lung function in CHF patients are due to the consequences of left atrial overload. Twenty-one CHF patients and six healthy subjects (Ctrl) participated in this study. Transfer lung capacity for carbon monoxide (T(LCO)) and maximal expiratory flows (V (max)) were measured before a maximal exercise test and 1h, 2h and 20h afterwards. CHF patients were divided in two groups according to their ventilatory response to the maximal exercise test (V(E) vs. V(CO(2)) relationship slopes above or below 34, i.e., CHF>34 and CHF<34). Compared with the Ctrl group, in CHF groups resting T(LCO) and V(max) were lower. After exercise, further changes in T(LCO) and V(max) were observed in CHF>34. T(LCO) per unit volume (K(CO)) was increased 1h post-exercise while maximal expiratory flow between 25 and 75% of forced vital capacity was decreased 2h and 20h post-exercise. We observed a negative correlation between the delta T(LCO) 1h post-exercise from rest and the delta T(LCO) 2h post-exercise from rest. The decreases in pulmonary V(max) we observed well after exercise following increases in K(CO) in patients with high ventilatory response to exercise (CHF>34) might indicate bronchial congestion resulting from increased left atrial pressure during exercise. We propose that endurance training should be prescribed cautiously for these patients.

Can bronchodilator response predict bronchial response to methacholine in preschool coughers?

The aim of the present study was to determine the relationship between bronchodilator response, assessed by interrupter resistance (Rint), and bronchial reactivity in preschool children with chronic cough. Thirty-eight children coughers (median age 5.0 years, range 2.8-6.4) were tested. Bronchodilator response was recorded within 4 months before methacholine challenge. Response to the latter was assessed using transcutaneous partial pressure of oxygen and Rint. Children were considered responders if a 20% fall in transcutaneous partial pressure of oxygen occurred during the bronchial challenge. Bronchodilator response was not different between responders (n = 24) and nonresponders (n = 14) [median (range) -0.11 (-0.44-0.09) vs. -0.08 (-0.21-0.10) kPa L(-1) sec; respectively]. However, none of the nonresponders had a bronchodilator response larger than -0.21 kPa L(-1) sec, this cutoff had a 100% positive and a 44% negative predictive value to predict a positive methacholine challenge. The relationship between bronchodilator response and bronchial methacholine responsiveness reached the limit of significance (P = 0.048). Furthermore, the magnitude of the bronchodilator response was correlated to the level of methacholine-induced level of bronchoconstriction (P = 0.01), and to the postchallenge bronchodilation (P = 0.04), all values expressed as % predicted. Moreover, the postbronchodilator Rint value obtained with preceding methacholine challenge was lower than the postbronchodilator value without preceding methacholine challenge in 71.4% (10/14) of the nonresponders and in only 33.3% (8/24) of the responders. Conclusions in preschool coughers bronchodilator response, assessed by the interrupter technique, was correlated to the bronchial responsiveness to methacholine. Non responders had a bronchodilator response not larger than -0.21 kPa L(-1) sec.

Resting echocardiographic assessments of left atrial function and filling pressure interest in the understanding of exercise capacity in patients with chronic congestive heart failure.

OBJECTIVE: Doppler echocardiography is well recognized as the primary noninvasive imaging technique to assess global and regional cardiac function. Cardiopulmonary exercise testing has become a powerful tool to predict outcome in chronic heart failure (CHF). We looked for cardiac determinants, using resting echocardiographic parameters, of exercise tolerance in patients with CHF. METHODS: Transthoracic echocardiography and standardized cardiopulmonary exercise testing were performed in 75 patients (59 +/- 11 years) with CHF, New York Heart Association functional class II to III. Systolic and diastolic function, filling pressures, and left ventricular, right ventricular, and left atrial (LA) regional function were assessed using Doppler tissue velocities and strain values. RESULTS: Maximal workload (86 +/- 41 W) and peak oxygen (14.6 +/- 3.1 mL/min/kg) correlated with left ventricular filling pressure estimates (E/Ea and E/Vp) but also with end-diastolic pulsed Doppler tissue velocity at the mitral annulus (Aa), LA volume, and regional LA function assessed by strain analysis. In multivariate analysis, maximum workload and peak oxygen were shown to correlate with right ventricular peak strain, although Aa and E/Ea were the best predictors of exercise capacity. CONCLUSION: Capacity to exercise in patients with CHF is understandable by resting echocardiography. Filling pressures, and LA and right ventricular functions, are its cardiac best determinants. Adding Aa peak velocity in resting echocardiographic evaluation of patients with CHF is found useful.

Interrupter resistance short-term repeatability and bronchodilator response in preschool children.

UNLABELLED: Interrupter resistance (Rint) technique can be easily and successfully performed in preschool children. The establishment of Rint short-term repeatability is essential to interpret any Rint change after a pharmacological intervention. AIMS OF THE STUDY: In preschool children with asthma or chronic cough: (1) to assess two indices of short-term repeatability: (a) intra-measurement and (b) within-occasion between-test repeatability; (2) to study the relationship between short-term repeatability and bronchodilator response (BDR). RESULTS: Rint intra-measurement repeatability assessed by the coefficient of variation was similar at baseline and after bronchodilator in asthmatics and in coughers (median 10% and 12%, respectively). There was no significant difference between asthmatics and coughers for both coefficient of repeatability (CR) (0.25 kPa L(-1)s and 32% of predicted vs 0.16 kPa L(-1) s and 21% of predicted, respectively) and BDR (median -14.7% vs -21.1% of predicted, respectively). However, in 20% of the study children, baseline variability of Rint modified the significance of the BDR. CONCLUSION: In the present study, Rint short-term repeatability was similar to that of previous studies. Similar Rint repeatability in coughers and in asthmatic children favored the use of asthmatic CR for both populations, and a -35% cut-off as a positive BDR. In 20% of study children, baseline Rint variability could influence the significance of the BDR. In order to improve assessment of BDR using Rint, further studies are needed (1) to compare the variability of Rint to other resistance measurement techniques and (2) to define the best method for Rint calculation and for expression of BDR.

Echocardiographic right ventricular strain analysis in chronic heart failure.

OBJECTIVE: We sought to compare the additive value of right ventricular (RV) function assessed by longitudinal systolic strain (epsilon% - ROI: 9.2 at 10.8 mm) with cardiopulmonary exercise testing (CPET) or brain natriuretic peptide (BNP) in patients with heart failure (HF). METHOD: We studied 19-patients (age = 56 +/- 8 years) in New York Heart Association HF class III-IV, who underwent standard and tissue Doppler echocardiography, CPET and BNP measurements on the same day. RV function was assessed by systolic strain (epsilon, %, ROI: 9.2-10.8 mm) in the mid-segment. Clinical outcomes were examined at 6 months. RESULTS: epsilon (-19.9+/-6.8%) was correlated with BNP (R = 0.52, P = 0.02), slope VE/VCO(2) (R = -0.65, P = 0.003), peak VO(2) (R = 0.46, P = 0.04) and the maximal workload (Watts) developed during CPET (R = 0.54, P=0.02). During follow-up, 1-patient died, 1-underwent heart transplantation, and 4 were re-hospitalized for worsening HF. Patients with major adverse cardiac events (MACE) had a significantly higher mean BNP concentration (852.8 ng/mL +/- 1114.3 vs. 201.4+ /- 293.8, P = 0.03), higher VE/VCO(2) (41.3 +/- 3.6 vs. 35.0 +/- 4.8 P < 0.001) and lower epsilon (-13.9 +/- 4.9 vs. -22.2+ /- 5.8, P < 0.001) than patients who remained MACE-free. By multivariate analysis, ST was the only predictor of MACE. CONCLUSION: In HF-patients presenting, RV-function assessed by systolic epsilon was reliable, easily measurable and a stronger prognosticator than CPET or BNP.

Spectral analysis of heart rate variability: interchangeability between autoregressive analysis and fast Fourier transform.

Interchangeability between fast Fourier transform (FFT) and autoregressive (AR) analysis was assessed on series of 256 R-R intervals recorded in 56 seated subjects and in 15 men performing an orthostatic test. Low- (LF) and high-frequency (HF) components were calculated and expressed both in absolute (square milliseconds) and normalized units (NU). During orthostatic stress, the same upward trend for LF square milliseconds and LF/HF ratio and downward trend for HF square milliseconds and HF NU were observed with FFT and AR analysis. However, the values for HF square milliseconds were significantly greater with FFT, as compared with AR analysis in standing position (P < .05). Moreover, Bland & Altman method highlighted a large discrepancy between the results of FFT and AR analysis for all heart rate variability indices in the 3 conditions. Therefore, parametric and nonparametric spectral analyses could not be considered as interchangeable at rest in healthy subjects even if they give same qualitative results.

A distributional analysis of the effect of physical exercise on a choice reaction time task.

The aim of this study was to examine the facilitating effects of physical exercise on the reaction process. Eleven participants with specific expertise in decision-making sports performed a choice reaction time task during moderate sub-maximal exercise (90% of their ventilatory threshold power). Participants were tested at rest and while cycling. During exercise, the participants were faster, without being more variable. We suggest that the effect of exercise on cognitive performance was due to a major generalized improvement of the whole distribution of response time and, although the benefit effect was small, it was consistent throughout the entire range of reaction times.

Effect of Nomega-nitro-L-arginine methyl ester-induced intrauterine growth restriction on postnatal lung growth in rats.

Infants with intrauterine growth restriction (IUGR) are at high risk for morbidity and mortality. Preeclampsia, one of the leading causes of IUGR, begins during the canalicular phase of lung development. The aim of our study was to determine whether induced IUGR was responsible for abnormal lung development in rat pups. We randomized pregnant Sprague-Dawley rats to daily gavage with either the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME; n = 5, 50 mg . kg(-1) . d(-1)) or pure water (n = 6). The pups were weighed at birth and on postnatal days 7 and 14. At each of these time points, pups were killed and their lung growth was assessed on the basis of lung volume and light-microscopy morphometric data. At birth, body weight, total alveolar surface area, and alveolar surface density were significantly decreased and alveolar size was significantly increased in the L-NAME group, compared with the control group. On day 7, body weight was similar in the two groups, and the only significant difference was smaller total alveolar surface area in the L-NAME group. On day 14, neither body weight nor lung morphometric parameters were significantly different between the L-NAME group and the controls. These results suggest that postnatal catch-up growth may completely correct the lung development disorders present at birth in IUGR pups, in parallel with the catch-up body weight gain.

Parasympathetic airway response and heart rate variability before and at the end of methacholine challenge.

BACKGROUND: The autonomic nervous system plays a primary role in regulating airway caliber, and its dysfunction is likely to contribute to the pathogenesis of airways diseases. Moreover, some findings support the hypothesis that autonomic dysfunction and/or dysregulation contributes to the pathogenesis of airway hyperresponsiveness (AHR). Heart rate variability (HRV) spectral analysis allows identifying noninvasively perturbations of the autonomic system. PURPOSES: We tested the relationship between AHR and cardiac parasympathetic tone assessed by HRV spectral analysis in patients submitted to a diagnostic methacholine bronchial challenge (MBC). METHODS: Fifteen women and 38 men (age range, 18 to 56 years) participated in the study. The principal indications for MBC were suspected asthma, chronic cough, unexplained exercise-induced dyspnea, or cough. The R-R intervals were continuously recorded during the MBC. Autoregressive method was performed on two series of 256 R-R intervals extracted before and after the MBC to obtain low-frequency (LF) and high-frequency (HF) components. RESULTS: The MBC distinguished 29 subjects without airway responsiveness (R-) and 24 responder or hyperresponsive subjects (R+): mean provocative dose of methacholine causing a 20% reduction in mean (+/- SD) FEV1 of 467 +/- 351 microg (range, 70 to 1,426 microg). The HF component expressed in normalized units (n.u.) [the index of parasympathetic modulation] was significantly higher in R+ than in R- at baseline, before MBC (21 +/- 21 n.u. vs 11 +/- 9 n.u., p < 0.05). Interestingly, R+ showed a significant increase of HF component after MBC (243 +/- 30 to 567 +/- 620 ms2 and 21 +/- 21 to 34 +/- 30 n.u., p < 0.01). For all subjects, HF (n.u.) calculated at baseline and after MBC were significantly influenced by the bronchial responsiveness (r2 = -0.28 and -0.51, respectively; p < 0.001). CONCLUSION: In summary, we found that R+ had a significantly higher parasympathetic tone than R- at baseline, and that R+ showed a significant increase in cardiac reactivity after bronchial challenge. These findings demonstrate that the autonomic nervous system, which contributes to the pathogenesis of AHR, is closely linked to cardiac modulation.

Spectral analysis of heart rate variability during exercise in trained subjects.

PURPOSE: To investigate the effects of strenuous exercise on heart rate variability (HRV). METHODS: We evaluated the effects of exercise intensity and duration on HRV indices in 14 healthy trained subjects. Each subject exercised for 3, 6, and 9 min at 60 and 70% of the power achieved at maximal oxygen consumption (PVO2(max)) and for 3 and 6 min (or 3 min twice) at 80% of PVO2(max). The electrocardiogram RR intervals were recorded then processed by fast(FFT) and short-time (STFT) Fourier transform for determination of low-frequency (LF, 0.045-0.15 Hz) and high-frequency (HF, 0.15-1.0 Hz) components. RESULTS: The LF and HF components expressed as absolute power (ms2) decreased significantly at the onset of exercise (P < 0.05). However, with increasing exercise intensity, the HF component expressed as normalized units (n.u.) (reflecting parasympathetic modulation) increased significantly, whereas the LF component (n.u.) and LF/HF ratio (both reflecting sympathetic modulation) decreased significantly (P < 0.05). STFT showed that increasing exercise intensity was associated with a shift in HF peak frequency related to an increase in respiratory rate and a marked decrease in LF power (ms2). Moreover, HFn.u. rose (r = 0.918, P < 0.01) and LFms2 fell as minute ventilation increased (r = 0.906, P < 0.01). CONCLUSIONS: Parasympathetic respiratory control and nonautonomic mechanisms may influence the HF-peak shift during strenuous exercise. HRV and the usual indexes of sympathetic activity do not accurately reflect changes in autonomic modulation during exhaustive exercise.

[Sports and cardiorespiratory function]. / Sport et fonction cardio-respiratoire.

Regular physical training is generally considered to help prevent numerous diseases. These beneficial effects of aerobic exercise are particularly well established with regard to cardiovascular and respiratory functions. However, exhaustive exercise is clearly a risk in some athletes who have not undergone a correct and complete assessment of cardiovascular and respiratory functions. Exercise training is a crucial tool in integrative rehabilitation programs for patients with chronic heart failure and respiratory diseases.