Cyril Schweitzer

Respiratory impedance response to a deep inhalation in asthmatic children with spontaneous airway obstruction

The aim of the study was to determine whether the bronchomotor effect of a deep inhalation (DI) may be detected during tidal breathing in asthmatic children with spontaneous airway obstruction (AO). Two groups of children aged 5–15 yrs were studied. AO was mild in group 1 (n=12, forced expiratory volume in one second (FEV1) ≥75% predicted) and moderate-to-severe in group 2 (n=9, FEV1 ≤70% pred). The forced oscillation technique at 12 Hz using a head generator allowed the determination of respiratory resistance in inspiration (Rrsi) and expiration (Rrse) before and after DI, at baseline and after salbutamol. At baseline, Rrsi but not Rrse was found to decrease significantly after DI in group 1 but not in group 2. The change induced by DI was significantly different in group 1 (−1.5±0.5 hPa·s·L−1) compared to group 2 (0.5±0.5 hPa·s·L−1) and exhibited significant negative correlation to FEV1 % pred. After salbutamol, DI had no effect. In conclusion, asthmatic children show a bronchomotor response to deep inhalation that depends on the degree of airway obstruction. The effect is more readily demonstrated in inspiration than in expiration.

Estimation of the bronchodilatory effect of deep inhalation after a free run in children

The bronchomotor effects of a deep inhalation (DI) may provide relevant information about the mechanisms of exercise-induced airway obstruction in children and may be assessed by respiratory conductance (Grs) measured using the forced oscillation technique. The aims of the present study were to assess the effect of DI on Grs after exercise in relationship to the lung function response to exercise. Grs at 12 Hz using a head generator and spirometric data were measured in 62 children suspected of asthma before and 5 min after a 6-min free run. After exercise, Grs was significantly increased by DI in 38 subjects, who also showed larger Grs and forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) responses to exercise than the 24 nonresponders. Stepwise regression indicated significant correlation between the response of Grs to DI and both Grs and FEV1/FVC responses to exercise. The data are consistent with exercise-induced bronchoconstriction being reversed by deep inhalation.

Respiratory conductance response to a deep inhalation in children with exercise-induced bronchoconstriction

Airway response to deep inhalation (DI) may provide information relevant to the mechanisms of airway obstruction (AO). The hypothesis examined here is that DI provokes bronchodilation in children during exercise-induced bronchoconstriction (EIB). EIB was attested in 15 children aged 10+/-3 year (mean+/-SD) by a decrease in forced expiratory volume in 1 s (FEV1) > or = 15% from baseline after a free running test. The respiratory resistance was measured by the forced oscillation technique at 12 Hz using a head generator to vary transrespiratory pressure around the head. The airway response to DI was estimated by the effect on respiratory conductance (Grs), calculated as the reciprocal of respiratory resistance in inspiration. During EIB, DI induced a variable but significant increase in Grs, from 0.085+/-0.023 to 0.101+/-0.029 l hPa(-1) s(-1) (P = 0.0003). The post- to pre-DI Grs ratio (1.19+/-0.14) was found to correlate negatively with EIB-induced reduction in FEV1 (P = 0.02), forced vital capacity (FVC) (P = 0.01) but not FEV1/FVC, i.e., DI induced more bronchodilation in those children with small EIB associated reduction in FVC. It is concluded that the bronchodilator effect of DI may be demonstrated in children with EIB. It is suggested that the associated small airway closure and lung hyperinflation may contribute to limit this response to DI.

Effect of Nebulized Hypertonic Saline Treatment in Emergency Departments on the Hospitalization Rate for Acute Bronchiolitis: A Randomized Clinical Trial

Importance Acute bronchiolitis is the leading cause of hospitalization among infants. Previous studies, underpowered to examine hospital admission, have found a limited benefit of nebulized hypertonic saline (HS) treatment in the pediatric emergency department (ED). Objective To examine whether HS nebulization treatment would decrease the hospital admission rate among infants with a first episode of acute bronchiolitis. Design, Setting, and Participants The Efficacy of 3% Hypertonic Saline in Acute Viral Bronchiolitis (GUERANDE) study was a multicenter, double-blind randomized clinical trial on 2 parallel groups conducted during 2 bronchiolitis seasons (October through March) from October 15, 2012, through April 15, 2014, at 24 French pediatric EDs. Among the 2445 infants (6 weeks to 12 months of age) assessed for inclusion, 777 with a first episode of acute bronchiolitis with respiratory distress and no chronic medical condition were included. Interventions Two 20-minute nebulization treatments of 4 mL of HS, 3%, or 4 mL of normal saline (NS), 0.9%, given 20 minutes apart. Main Outcomes and Measures Hospital admission rate in the 24 hours after enrollment. Results Of the 777 infants included in the study (median age, 3 months; interquartile range, 2-5 months; 468 [60.2%] male), 385 (49.5%) were randomized to the HS group and 387 (49.8%) to the NS group (5 patients did not receive treatment). By 24 hours, 185 of 385 infants (48.1%) in the HS group were admitted compared with 202 of 387 infants (52.2%) in the NS group. The risk difference for hospitalizations was not significant according to the mixed-effects regression model (adjusted risk difference, –3.2%; 95% CI, –8.7% to 2.2%; P = .25). The mean (SD) Respiratory Distress Assessment Instrument score improvement was greater in the HS group (–3.1 [3.2]) than in the NS group (–2.4 [3.3]) (adjusted difference, –0.7; 95% CI, –1.2 to –0.2; P = .006) and similarly for the Respiratory Assessment Change Score. Mild adverse events, such as worsening of cough, occurred more frequently among children in the HS group (35 of 392 [8.9%]) than among those in the NS group (15 of 384 [3.9%]) (risk difference, 5.0%; 95% CI, 1.6%-8.4%; P = .005), with no serious adverse events. Conclusions and Relevance Nebulized HS treatment did not significantly reduce the rate of hospital admissions among infants with a first episode of acute moderate to severe bronchiolitis who were admitted to the pediatric ED relative to NS, but mild adverse events were more frequent in the HS group. Trial Registration clinicaltrials.gov Identifier: NCT01777347

Within breath ventilatory responses to mechanical tracheal stimulation in anaesthetised rabbits.

Ventilatory responses to airway mechanical stimulation usually consist in mixed cough (CR) and expiration (ER) reflexes. The stimulus characteristics that would favour either reflex may vary with breathing, but the issue cannot be addressed with the usual long lasting stimulus. The aim of the study was to describe respiratory responses evoked by a punctuate tracheal stimulus and their relationship to inspiration and expiration. Experiments were repeated after bronchoconstriction. Eight anesthetized tracheotomized rabbits were stimulated in the trachea by 150 ms probing before and after methacholine inhalation (248 tests). CR and ER were evaluated from tidal volume and expiratory flow. The overall incidence of responses was larger in inspiration than expiration (p < 0.0001). A majority of responses were single CR or ER, also strongly related to breathing: 93% CR occurred with the stimulus in inspiration and 78% ER with the stimulus in expiration (p = 0.001). Bronchoconstriction did not change the incidence of single efforts, increased that of mixed responses and decreased the amplitude of preparatory and expulsive phases of CR. The study demonstrates the strong dependence of CR and ER on the phase of breathing and adds to the current evidence that regulating mechanisms clearly differ for each reflex.

Identification of Bronchodilator Responsiveness by Forced Oscillation Admittance in Children

The upper airway wall motion may be responsible for significant error when measuring respiratory resistance (Rrs) with the forced oscillation technique (FOT), particularly in young children with airway obstruction. Assessing the response to methacholine from the change in respiratory admittance (Ars, the reciprocal of respiratory impedance, Zrs) avoids the artifact. The aim of the study was to explore the possibility of assessing the response to a bronchodilator from the change in Ars. FOT measurements were performed at 12 Hz in 36 young children before and after salbutamol. Transrespiratory pressure was varied in two ways: directly at the mouth (standard generator, SG) and around the head (head generator, HG), a variant nearly free of upper airway artifact. Salbutamol induced significantly lower Rrs and Zrs change with SG than HG (respectively, p = 0.0003 and 0.05). The relative change in Ars was not significantly different with SG and HG. Both estimates were significantly correlated (p < 0.0001). The change in Ars may thus be useful to avoid the upper airway artefact when assessing the response to salbutamol using the FOT in young children.

Deep inhalation prevents the respiratory elastance response to methacholine in rats

The bronchodilator effect of deep inhalation (DI) may be assessed from the time course of respiratory system resistance (Rrs) and reactance (Xrs) measured by the forced oscillation technique at a single frequency. The aim of the study was to assess the effect of DI in the closed chest rat. Under anesthesia and mechanical ventilation, seven Brown Norway rats were given regular DI (BN-di) and six underwent continuous tidal ventilation (BN) throughout an otherwise similar methacholine (Mch) challenge protocol. Rrs and Xrs were monitored at 20 Hz and apparent respiratory system elastance (Ers) was computed from Xrs. After Mch nebulization, there was a significant increase in Rrs and Ers compared with saline. Ers, but not Rrs, decreased after the DI and BN-di were found to have lower Ers than BN. Thus, DI significantly alters Ers and its response to Mch. Computer simulations suggested reversal of increased viscoelasticity and/or inhomogeneous behavior by the DI in that model.

De novo complex X chromosome rearrangement unmasking maternally inherited CSF2RA deletion in a girl with pulmonary alveolar proteinosis.

We report on a 3‐year‐old girl with a de novo complex X chromosome rearrangement associated with congenital pulmonary alveolar proteinosis (PAP) and short stature. Array comparative genome hybridization and FISH analyses contributed to characterize the complex rearrangement consisting of a 7.37 Mb terminal deletion of Xp22.33p22.2, a 17.3 Mb interstitial inverted duplication of Xp22.2p21.3, and a 10.14 Mb duplication of Xq27.3q28. PCR analysis of microsatellite markers supported a paternal origin of the X chromosome rearrangement. A pre‐meiotic two‐step mechanism may explain the occurrence of this complex X rearrangement: an inverted duplication deletion event on Xp, and duplication of the Xq27.3qter region through a telomere capture event stabilizing the broken chromosome Xp end. The girl has also inherited from her healthy mother an X chromosome with a colony stimulating factor 2 receptor, alpha (CSF2RA) gene deletion. Consistent with the recessive mode of inheritance, the de novo paternal Xp22.33p22.2 deletion combined to the maternally inherited CSF2RA gene deletion led to homozygous deletion of CSF2RA and PAP diagnosis in the girl. The Xp deletion encompasses the pseudoautosomal region 1 (PAR1) which contains genes that escape X inactivation. Short stature homeobox (SHOX) haploinsufficiency explains growth retardation. Absence of other symptoms in relation to the X deletion/amplification is most probably due to skewed X inactivation. Finally, inherited deletions may unmask rare pathogenic genomic rearrangement and contribute to clinical phenotypes by a recessive mode of gene action.

Airway response to induced muscular contraction in spontaneously breathing rabbits

The airways are thought to dilate during exercise in humans but the time course and mechanisms of the response are not fully described. The aim of the study was to document changes in airway calibre during electrically induced muscular contractions (MC) in spontaneously breathing rabbits. Experiments were also performed after induced bronchoconstriction to assess the effect of change in breathing pattern on airway calibre during MC. Respiratory resistance (R(RS)) was measured in 12 rabbits using the forced oscillation technique at 20 Hz before, during and after 30s MC in control conditions and after methacholine induced bronchoconstriction (Mch). MC was associated with significant decrease in R(RS) both at control and Mch. The MC induced increase in V(E) occurred with significant albeit small change in mean tidal volume (V(T)) at Mch but not control. An augmented breath (AB) occurred in 29/35 MCs and was usually associated with an abrupt drop in R(RS). The decrease in R(RS) induced by AB was significantly larger at Mch compared with control. Passively inflating the lung after MC induced significantly larger decrease in R(RS) than AB during MC. The data indicate bronchodilation by MC in spontaneously breathing rabbits. The mechanisms appear to include AB dependent airway wall stretching as well as removal of cholinergic input to the airway smooth muscle.

Exercise-induced bronchoconstriction in school-age children born extremely preterm

Background:School children born preterm often show airway hyperresponsiveness to methacholine or histamine. Less attention has been paid to their airway response to exercise, an important point because of the role of exercise in the child’s daily life. The aim of this study was to describe the characteristics of, and potential determinants to, the airway response to exercise in children born extremely preterm.Methods:Forty-two nonasthmatic nonatopic children born before 32 wk gestation were compared with 27 healthy nonasthmatic nonatopic term children at age 7. Spirometry and respiratory impedance were measured at baseline and repeated after a single-step 6-min treadmill exercise in a climate-controlled room.Results:The preterm group showed significant broncho-constriction induced by exercise. Prematurity, but not low baseline lung function, neonatal oxygen supplementation, mechanical ventilation, chronic lung disease, or maternal smoking, was a determinant of exercise-induced bronchoconstriction.Conclusion:Children born extremely preterm present significant exercise-induced airway obstruction at age 7. The response has different characteristics from that occurring in asthmatics and is likely to express airway noneosinophilic inflammation.