Cross-sectional phenotyping of small airway dysfunction in preschool asthma using the impulse oscillometry system.

Objective. Asthma is a chronic inflammatory airway disorder known to induce small airways dysfunction (SAD). It is important to develop tools to assess the presence and extent of SAD in daily clinical practice. An Impulse Oscillometry System (IOS) might detect SAD, but the validity of the underlying model (serial Resistive airway and Compliant tissue model: RC model) in diseased lungs remains questionable.Methods. Our objective was to evaluate the usefulness of parameters obtained from six electrical circuit models that were fitted to the measurements of impedance obtained with IOS in asthmatic children characterized by an abnormal lung function defined by an increased baseline interrupter resistance (Rint, z-score > +1.645).Results. The six models were tested in 102 asthmatic children (median age: 5.5 years). Two models allowed the description of 92/102 (90%) children: 74 by the extended RIC model (central and peripheral Resistance, Inertance and peripheral airway Compliance) and 18 by the Mead1969 model (extended RIC plus lung compliance). Thus, peripheral airway compliance and resistance were essential to describe lung function abnormalities of these asthmatic children. Parenchyma impairment (increased lung compliance) which was responsive to salbutamol was present in 18% of asthmatic children. After salbutamol, peripheral airway resistance decreased while peripheral airway compliance increased, arguing for asthma-related SAD. R5-20Hz independently correlated with the two latter parameters but was increased in two thirds of children with increased Rint only.Conclusion. Additional modeling of IOS results can be a reliable tool to assess the presence and extent of SAD in young asthmatic children.

Salbutamol Worsens the Autonomic Nervous System Dysfunction of Children With Sickle Cell Disease.

BACKGROUND: Sickle cell disease (SCD) patients with asthma have an increased rate of vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) episodes when compared to those without asthma. We hypothesized that either asthma diagnosis or bronchodilator treatment might aggravate SCD via their modulating effect on the autonomic nervous system (ANS). METHODS: Cross-sectional evaluation of heart rate variability (HRV) during pulmonary function tests, including salbutamol administration, in children with SCD receiving asthma treatment or not when compared to asthmatic children without SCD matched for ethnicity. RESULTS: SCD children with asthma (n = 30, median age of 12.9 years old) were characterized by a reduced FEV1/FVC ratio, an increased bronchodilator response, and a greater incidence of VOC and ACS when compared to SCD children without asthma (n = 30, 12.7 years). Children with asthma without SCD (n = 29, 11.4 years) were characterized by a higher exhaled NO fraction than SCD children. SCD children when compared to non-SCD children showed reduced HRV [total power, low (LF) and high (HF, vagal tone) frequencies], which was further worsened by salbutamol administration in all the groups: reduction in total power and HF with an increase in LF/HF ratio. After salbutamol, the LF/HF ratio of the SCD children was higher than that of the non-SCD children. The two groups of SCD children were similar, suggesting that asthma diagnosis per se did not modify ANS functions. CONCLUSION: SCD children are characterized by impaired parasympathetic control and sympathetic overactivity that is worsened by salbutamol administration. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT04062409.

Cross-sectional study of loop gain abnormalities in childhood obstructive sleep apnea syndrome.

STUDY OBJECTIVES: We aimed to assess ventilatory control in typically developing children with and without obstructive sleep apnea (OSA). METHODS: Otherwise healthy children referred for suspicion of OSA were recruited. In addition to polysomnography, we analyzed loop, controller and plant gains (ie, LG, CG, and PG), which reflect the stability of control, chemoreceptor sensitivity and the pulmonary control of blood gases in response to changes in ventilation, respectively, from tidal breathing recordings during wakefulness. Two bivariate (ventilation, end-tidal CO2: one unconstrained and one constrained) and one trivariate (plus end-tidal oxygen) unconstrained model were used to assess model consistency and oxygen chemosensitivity. RESULTS: In sum, 54 children (median age 11.6 years) were included. Children with OSA (n = 19, [obstructive apnea-hypopnea index] OAHI ≥2.h-1) had a higher plant gain compared with those without OSA (n = 35), and it was positively correlated with apnea hypopnea index (AHI) (r2 = 0.10, p < 0.020). The two models showed consistent results. The bivariate constrained model showed that children with OAHI ≥5.h-1 showed an increased steady-state plant gain compared with children with OAHI <5.h-1. The trivariate model did not show evidence of any abnormality of oxygen chemosensitivity. CONCLUSION: Plant gain may contribute to OSA pathophysiology in children, and therapies directed at its reduction should be tested.

The utility of acoustic pharyngometry and rhinometry in pediatric obstructive sleep apnea syndrome.

OBJECTIVE: Our objective was to evaluate the usefulness of acoustic pharyngometry and rhinometry in assessing obstructive sleep apnea (OSA) syndrome in children. PATIENTS/METHODS: Patients who were hospitalized for polysomnography underwent acoustic pharyngometry and rhinometry in sitting and supine positions to measure anatomical (pharyngeal and nasopharyngeal) volumes and collapsibility characteristics (reduction of pharyngeal volume, estimated pharyngeal compliance, and reduction of nasopharyngeal volume). RESULTS: In this study, we prospectively enrolled 103 children (median age, 10.4 years; 47 girls). Measures obtained from rhinometry correlated with height and were further height-normalized whereas measures obtained from pharyngometry did not correlate with height. Sleep apnea was ruled out in 51 subjects, while 52 children fulfilled OSA criteria (35 with obstructive apnea-hypopnea index ≥ 2 and < 5.h-1 [mild] and 17 with an index ≥ 5). The three groups differed on the z-score of BMI, the reduction of pharyngeal volume when supine, the estimated pharyngeal compliance and the supine normalized nasopharyngeal volume. These four factors linearly correlated with the apnea index even though children without OSA and mild OSA were found to be similar overall. A multivariate analysis with apnea index as the dependent variable and BMI z-score, neck circumference, mean pharyngeal area in supine position, estimated pharyngeal compliance and normalized nasopharyngeal volume as independent variables, showed that only BMI z-score and estimated compliance remained independent predictors of obstructive apnea (r2 value = 0.25, p < 0.0001). CONCLUSION: An increase in pharyngeal compliance is an independent risk factor of OSA syndrome in children; it can be measured using acoustic pharyngometry while awake.

Pulse wave amplitude reduction as a surrogate for cortical arousal during sleep hypopnea in children.

OBJECTIVES: The accuracy of respiratory polygraphy (RP) is limited because of the absence of electroencephalography (EEG). Pulse wave amplitude (PWA) reduction has been shown to be a marker of autonomic activation during arousal, and may represent a substitute for obstructive respiratory-related cortical arousal (RRCA). This study tested the hypothesis that PWA could be a surrogate for RRCA in detecting obstructive hypopnea (OH) in a pediatric population. MATERIALS AND METHODS: Two experienced readers scored 30 consecutive polysomnographies (PSG) using standard scoring rules. Automatic software detected every 20-90% reduction in PWA. A second scoring of respiratory events using PWA reduction as a surrogate for RRCA was performed (RP with PWA) for each percentage of PWA reduction. The final analysis consisted of determining the concordance between the two methods of detecting OH. RESULTS: A total of 987 episodes of ≥30% flow reduction were analyzed: 330 with RRCA only, 205 with desaturation (DS) only, 134 with both, and 318 without RRCA or DS. As the percentage of reduction in PWA increased, the sensitivity of PWA as a substitute for RRCA decreased, but the specificity increased. For a decrease in PWA of 60% or 70%, the sensitivities of PWA as a substitute for RRCA were 79% and 57%, and the specificities 51% and 76%, respectively. CONCLUSION: Pulse wave amplitude reduction lacks sensitivity and specificity to be used as a surrogate for RRCA to detect OH in children. Polysomnography remains the gold standard for the diagnosis of sleep disordered breathing in children.