Pediatric long-term noninvasive respiratory support in children with central nervous system disorders.

RATIONALE: The use of long-term noninvasive respiratory support is increasing in children along with an extension of indications, in particular in children with central nervous system (CNS) disorders. OBJECTIVE: The aim of this study was to describe the characteristics of children with CNS disorders treated with long-term noninvasive respiratory support in France. METHODS: Data were collected from 27 French pediatric university centers through an anonymous questionnaire filled for every child treated with noninvasive ventilatory support ≥3 months on 1st June 2019. MAIN RESULTS: The data of 182 patients (55% boys, median age: 10.2 [5.4;14.8] years old [range: 0.3-25]) were collected: 35 (19%) patients had nontumoral spinal cord injury, 22 (12%) CNS tumors, 63 (35%) multiple disabilities, 26 (14%) central alveolar hypoventilation and 36 (20%) other CNS disorders. Seventy five percent of the patients were treated with noninvasive ventilation (NIV) and 25% with continuous positive airway pressure (CPAP). The main investigations performed before CPAP/NIV initiation were nocturnal gas exchange recordings, alone or coupled with poly(somno)graphy (in 29% and 34% of the patients, respectively). CPAP/NIV was started in an acute setting in 10% of the patients. Median adherence was 8 [6;10] hours/night, with 12% of patients using treatment <4 h/day. Nasal mask was the most common interface (70%). Airway clearance techniques were used by 31% of patients. CONCLUSION: CPAP/NIV may be a therapeutic option in children with CNS disorders. Future studies should assess treatment efficacy and patient reported outcome measures.

Impact of Sleep Deprivation on Respiratory Motor Output and Endurance. A Physiological Study.

Rationale: Sleep deprivation can alter endurance of skeletal muscles, but its impact on respiratory command is unknown.Objectives: We aimed to assess the effect of sleep deprivation on respiratory motor output and inspiratory endurance.Methods: Inspiratory endurance was investigated twice in random order, following a normal sleep night and a sleepless night. Healthy participants were asked to breathe as long as possible until task failure against a moderate inspiratory threshold constraint. Transdiaphragmatic pressure and diaphragm electrical activity were measured throughout the trial to assess pressure output of the diaphragm and overall respiratory motor output. Cortical contribution to respiratory motor output was assessed by measurement of preinspiratory motor potential amplitude and by cervical magnetic simulation.Measurements and Main Results: Twenty healthy male participants were studied. Time to task failure was significantly shorter after sleep deprivation than after normal sleep: (30 min [interquartile range [IQR], 17-41] vs. 60 min [IQR, 45-60], P = 0.002). At the beginning of the trial, preinspiratory motor potential amplitude was significantly lower in the sleep-deprivation condition (4.5 µV [IQR, 2.5-6.4] vs. 7.3 µV [IQR, 4.3-10.4], P = 0.02) and correlated significantly with the duration of the endurance trial. In the sleep-deprivation condition, preinspiratory motor potential amplitude, electrical activity of the diaphragm, pressure output of the diaphragm, and Vt decreased and the respiratory rate increased significantly from the beginning to the end of the trial. Such decreases did not occur in the normal-sleep condition.Conclusions: One night of sleep deprivation reduces respiratory motor output by altering its cortical component with subsequent reduction of inspiratory endurance by half. These results suggest that altered sleep triggers severe brain dysfunctions that could precipitate respiratory failure.

Impact of sleep alterations on weaning duration in mechanically ventilated patients: a prospective study.

Sleep is markedly altered in intensive care unit (ICU) patients and may alter respiratory performance. Our objective was to assess the impact of sleep alterations on weaning duration.We conducted a prospective physiological study at a French teaching hospital. ICU patients intubated for at least 24 h and difficult to wean were included. Complete polysomnography (PSG) was performed after the first spontaneous breathing trial failure. Presence of atypical sleep, duration of sleep stages, particularly rapid eye movement (REM) sleep, and electroencephalogram (EEG) reactivity at eyes opening were assessed by a neurologist.20 out of 45 patients studied (44%) had atypical sleep that could not be classified according to the standard criteria. Duration of weaning between PSG and extubation was significantly longer in patients with atypical sleep (median (interquartile range) 5 (2-8) versus 2 (1-2) days; p=0.001) and in those with no REM sleep compared with the others. Using multivariate logistic regression analysis, atypical sleep remained independently associated with prolonged weaning (>48 h after PSG). Altered EEG reactivity at eyes opening was a good predictor of atypical sleep.Our results suggest for the first time that brain dysfunction may have an influence on the ability to breathe spontaneously.

Combined measurement of carbon monoxide and nitric oxide lung transfer does not improve the identification of pulmonary hypertension in systemic sclerosis.

Screening is important to determine whether patients with systemic sclerosis (SSc) have pulmonary hypertension because earlier pulmonary hypertension treatment can improve survival in these patients. Although decreased transfer factor of the lung for carbon monoxide (TLCO) is currently considered the best pulmonary function test for screening for pulmonary hypertension in SSc, small series have suggested that partitioning TLCO into membrane conductance (diffusing capacity) for carbon monoxide (DMCO) and alveolar capillary blood volume (VC) through combined measurement of TLCO and transfer factor of the lung for nitric oxide (TLNO) is more effective to identify pulmonary hypertension in SSc patients compared with TLCO alone. Here, the objective was to determine whether combined TLCO-TLNO partitioned with recently refined equations could more accurately detect pulmonary hypertension than TLCO alone in SSc.For that purpose, 572 unselected consecutive SSc patients were retrospectively recruited in seven French centres.Pulmonary hypertension was diagnosed with right heart catheterisation in 58 patients. TLCO, TLNO and VC were all lower in SSc patients with pulmonary hypertension than in SSc patients without pulmonary hypertension. The area under the receiver operating characteristic curve for the presence of pulmonary hypertension was equivalent for TLCO (0.82, 95% CI 0.79-0.85) and TLNO (0.80, 95% CI 0.76-0.83), but lower for VC (0.75, 95% CI 0.71-0.78) and DMCO (0.66, 95% CI 0.62-0.70).Compared with TLCO alone, combined TLCO-TLNO does not add capability to detect pulmonary hypertension in unselected SSc patients.

Circulating androgens in women: exercise-induced changes.

Physical exercise is known to strongly stimulate the endocrine system in both sexes. Among these hormones, androgens (e.g. testosterone, androstenedione, dehydroepiandrosterone) play key roles in the reproductive system, muscle growth and the prevention of bone loss. In female athletes, excessive physical exercise may lead to disorders, including delay in the onset of puberty, amenorrhoea and premature osteoporosis. The free and total fractions of circulating androgens vary in response to acute and chronic exercise/training (depending on the type), but the physiological role of these changes is not completely understood. Although it is commonly accepted that only the free fraction of steroids has a biological action, this hypothesis has recently been challenged. Indeed, a change in the total fraction of androgen concentration may have a significant impact on cells (inducing genomic or non-genomic signalling). The purpose of this review, therefore, is to visit the exercise-induced changes in androgen concentrations and emphasize their potential effects on female physiology. Despite some discrepancies in the published studies (generally due to differences in the types and intensities of the exercises studied, in the hormonal status of the group of women investigated and in the methods for androgen determination), exercise is globally able to induce an increase in circulating androgens. This can be observed after both resistance and endurance acute exercises. For chronic exercise/training, the picture is definitely less clear and there are even circumstances where exercise leads to a decrease of circulating androgens. We suggest that those changes have significant impact on female physiology and physical performance.

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.