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We aimed to compare cardiopulmonary exercise test (CPET) parameters, cardiac adaptations, and proportion of responders after different aerobic training programs amongst women and men with coronary heart disease (CHD). Patients with CHD were evaluated with a CPET and echocardiography before and after 3 months of aerobic exercise training. Peak oxygen uptake exercise training response was assessed according to the median peak oxygen uptake change for post- versus pretraining in the whole cohort (stratification non/low responders (NLR) vs. high-responders) and normalized for lean body mass (LBM). Eighty-three CHD patients were included (19 women, 64 men; 27 patients with interval, 19 with continuous, and 37 with combination exercises). Peak oxygen uptake, peak workload normalized for LBM, pulmonary variables (i.e., ventilation and oxygen uptake efficiency slope), and O2 pulse were significantly lower in women versus men. These parameters improved similarly with training in both sexes (p < 0.05). There were no differences in the proportion of NLR among women and men with CHD (7/19 (37%) vs. 35/64 (55%), p = 0.1719). Left ventricular ejection fraction and mean peak early diastolic mitral annulus velocity improved similarly with training in both sexes (p < 0.05). Women and men with CHD have a similar exercise training response regarding key CPET and echocardiographic parameters. The proportion of responders is similar. ClinicalTrials.gov: NCT03414996, NCT02048696, NCT03443193. Novelty: Cardiopulmonary adaptations to exercise training are similar among CHD men and women. Proportion of peak oxygen uptake for non/low/high responders is similar in CHD men and women. Left ventricular systolic and diastolic function improved similarly after exercise training in CHD men and women.

Introduction and objectives We compared the effects of 12 weeks of low-volume high-intensity interval training (LV-HIIT) vs moderate-intensity continuous exercise training (MICET) on cardiopulmonary exercise test parameters and the proportion of non/low responders (NLR) to exercise training in post-acute coronary syndrome (ACS) patients. Methods Patients with a recent ACS were randomized to LV-HIIT, MICET, or a usual care group. LV-HIIT consisted of 2 to 3 sets of 6 to 10 minutes with repeated bouts of 15 to 30 seconds at 100% of peak workload alternating with 15 to 30 seconds of passive recovery. Cardiopulmonary exercise test parameters were assessed, and key exercise variables were calculated. Training response was assessed according to the median VO2peak change post vs pretraining in the whole cohort (stratification NLR vs high response). Results Fifty patients were included in the analysis (LV-HIIT, n = 23; MICET, n = 18; usual care, n = 9) and 74% were male. The proportion of NLR was higher in the LV-HIIT group than in the MICET group (LV-HIIT 61%, MICET 21%, and usual care 80%; P = .0040). VO2peak-dependent variables (VO2peak, percent-predicted VO2peak) improved in both training groups (P = .002 and P Conclusions In patients with a recent ACS, several prognostic VO2peak-dependent variables were improved after LV-HIIT, but the improvement was more pronounced or only found after MICET. Low-volume HIIT resulted in a higher proportion of NLR than isocaloric MICET. Clinical trialsregistered at ClinicalTrials.gov (Identifiers: NCT03414996 and NCT02048696)

Resumen Introduccion y objetivos Se comparo los efectos de 12 semanas de ejercicio intervalico de alta intensidad y de bajo volumen (EIAI-BV) frente a un ejercicio continuo de intensidad moderada (ECIM), sobre los parametros de la prueba de esfuerzo cardiopulmonar y la proporcion de no respondedores o con baja respuesta (NBR) al ejercicio fisico en pacientes que sufrieron un sindrome coronario agudo (SCA). Metodos Se aleatorizo a pacientes con un SCA reciente a EIAI-BV, ECIM y a cuidados habituales. EIAI-BV consto de 2 a 3 sesiones de 6-10 minutos con periodos de repeticion de 15 a 30 s al 100% de la carga de trabajo alternados con 15-30 segundos de recuperacion pasiva. Los parametros de la prueba de ejercicio cardiopulmonar se evaluaron y se calcularon las variables claves. La respuesta al ejercicio se evaluo con la mediana de VO2 pico de cambio (post- frente a preejercicio) en toda la cohorte estratificada en NBR al ejercicio frente a alta respuesta. Resultados Se incluyo a 50 pacientes en el analisis (EIAI-BV, n = 23; ECIM, n = 18; cuidados habituales, n = 9), el 74% eran varones. La proporcion de NBR fue mayor en el EIAI-BV en comparacion con el grupo ECIM y el grupo de cuidados habituales (el 61 frente al 21 y el 80%, respectivamente; p = 0,0040). Las variables dependientes del VO2 (VO2 pico y porcentaje VO2 pico predicho) mejoraron en ambos grupos de entrenamiento (p = 0,002 y p Conclusiones En pacientes con un SCA reciente, varias variables pronosticas dependientes del VO2 pico mejoraron despues de EIAI-BV, pero la mejora fue mas pronunciada o bien mejoro unicamente despues de ECIM. El EIAI-BV resulto en una mayor proporcion de NBR en comparacion con el ECIM isocalorico. Ensayos registrados en ClinicalTrials.gov (Identificadores: NCT03414996 and NCT02048696)

Laryngeal and respiratory reflexes are vitally important defense mechanisms against foreign body aspiration, safeguarding airway patency, and ventilation. These highly preserved automatisms easily overrule external influences like willpower or (anesthetic) medication. Prevention and anticipation are, therefore, the essential strategies to avoid adverse events and damage, and treatment is most effective in the early stage of the reflex response. The physiology and pathophysiology of the various defensive reflexes as well as a comprehensive anesthetic approach to prevention and treatment are outlined in this review.

Background Apnea of prematurity cannot be reliably measured with current monitoring techniques. Instead, indirect parameters such as oxygen desaturation or bradycardia are captured. We propose a Kalman filter-based detection of respiration activity and hence apnea using multichannel esophageal signals in neonatal intensive care unit patients. Methods We performed a single-center observational study with moderately preterm infants. Commercially available nasogastric feeding tubes containing multiple electrodes were used to capture signals with customized software. Multichannel esophageal raw signals were manually annotated, processed using extended Kalman filter, and compared with standard monitoring data including chest impedance to measure respiration activity. Results Out of a total of 405.4 h captured signals in 13 infants, 100 episodes of drop in oxygen saturation or heart rate were examined. Median (interquartile range) difference in respiratory rate was 0.04 (−2.45 to 1.48)/min between esophageal measurements annotated manually and with Kalman filter and −3.51 (−7.05 to −1.33)/min when compared to standard monitoring, suggesting an underestimation of respiratory rate when using the latter. Conclusions Kalman filter-based estimation of respiratory activity using multichannel esophageal signals is safe and feasible and results in respiratory rate closer to visual annotation than that derived from chest impedance of standard monitoring.

Background Lung disease can develop within the first year of life in infants with cystic fibrosis (CF). However, the frequency and severity of respiratory symptoms in infancy are not known. Methods We assessed respiratory symptoms in 50 infants with CF and 50 healthy matched controls from two prospective birth cohort studies. Respiratory symptoms and respiratory rate were documented by standardized weekly interviews throughout the first year. Infants performed multiple breath washout in the first weeks of life. Results We analyzed 4552 data points (2217 in CF). Respiratory symptoms (either mild or severe) were not more frequent in infants with CF (OR:1.1;95% CI:[0.76, 1.59]; p=0.6). Higher lung clearance index and higher respiratory rate in infants with CF were not associated with respiratory symptoms. Conclusions We found no difference in respiratory symptoms between healthy and CF infants. These data indicate that early CF lung disease may not be captured by clinical presentation alone.

Linear aerobic training periodisation (LP) is recommended for patients with coronary heart disease (CHD). However, the effects of training periodisation on the right heart mechanics in patients with CHD have never been examined. This study aimed to explore the effects of LP and non-linear periodisation (NLP) on right heart mechanics. We prospectively randomised CHD patients to 12 weeks of aerobic training with LP or NLP. While there was a weekly increase in energy expenditure with LP, there was a steeper increase during the first 3 weeks, followed by a decrease in the fourth week with NLP. Echocardiography was performed at baseline and after the training period to assess the right ventricular free wall (RVFW) and right atrial strain. Thirty patients with CHD were included (NLP, n = 16; LP, n = 14). The traditional right and left heart parameters showed no significant time effects. There was a decrease of RVFW strain with time in both groups (+1.3 ± 0.9% with NLP, and +1.5 ± 0.8% with LP; p = 0.033). Mid-ventricular RVFW strain changed significantly with time (+2.0 ± 1.3% with NLP, and from +2.3 ± 1.2% with LP; p = 0.025). There was no time effect on the right atrial strain. In stable CHD patients, LP and NLP resulted in right ventricular strain decrements with a segment-specific pattern. This study was registered at ClinicalTrials.gov (identifier number: NCT03414996). Novelty: In stable coronary heart disease patients, both linear and non-linear aerobic training periodisation programs result in right ventricular strain decrements with time, particularly in the mid-ventricular segment. Traditional right and left heart parameters and right atrial strain showed no significant time effect in both 12 weeks aerobic training periodisation programs.

Background Aerobic exercise training is associated with beneficial ventricular remodeling and an improvement in cardiac biomarkers in chronic stable heart failure. High‐intensity interval training (HIIT) is a time‐efficient method to improve V˙O2peak in stable coronary heart disease patients. This pilot study aimed to compare the effect of HIIT on ventricular remodeling in patients with a recent acute myocardial infarction (AMI). Methods Nineteen post‐AMI patients were randomized to either HIIT (n = 9) or usual care (n = 10). A cardiopulmonary exercise test (CPET), transthoracic echocardiography, and cardiac biomarker assessment (ie, N‐terminal pro B‐type natriuretic peptide levels and G protein‐coupled receptor kinase 2 expression) were performed before and after a 12‐week training intervention. CPET parameters including oxygen uptake efficiency slope (OUES) and V˙O2 at the first ventilatory threshold (V˙O2 VT1) were calculated. left ventricular (LV) structural and functional echocardiographic parameters including myocardial strain imaging were assessed. Results V˙O2peak and OUES improved solely in the HIIT group (P

Objective: To compare the effects of high-intensity interval training versus moderate-intensity continuous training on risk markers of arrhythmic death in patients who recently suffered from an acute coronary syndrome. Design: Double-blind (patient and evaluator) randomized controlled trial. Setting: Cardiovascular Prevention and Rehabilitation Centre (EPIC Centre) of the Montreal Heart Institute, Montreal, Canada. Subjects: A total of 43 patients were randomized following an acute coronary syndrome. Interventions: Patients were assigned to either high-intensity interval training (n = 18) or isocaloric moderate-intensity continuous training (n = 19), three times a week for a total of 36 sessions. Main measures: Heart rate recovery for 5 minutes, heart rate variability for 24 hours, occurrence of ventricular arrhythmias, and QT dispersion were measured before and after the 36 sessions of training. Results: Among the 43 patients randomized, 6 participants in the high-intensity interval training group stopped training for reasons unrelated to exercise training and were excluded from the analyses. Heart rate recovery improved solely in the high-intensity interval training group, particularly at the end of recovery period ( p < 0.05). There were no differences in heart rate variability, occurrence of ventricular arrhythmias, or QT dispersion parameters between the groups at study end. Conclusion: Despite the lack of power to detect any large difference between the two interventions with respect to risk markers of arrhythmic death, high-intensity interval training appears safe and may be more effective at improving heart rate recovery relative to moderate-intensity continuous training in our patients following acute coronary syndrome.

A Child's Sleep: A Book with Seven Seals? A Guide to Systematic Problem Identification and Solution Abstract. The sleep of a child can be influenced and sometimes disturbed by many, often development-associated, phenomena. This results not only in a burden for the child, but regularly also for the parents, who in their need for help, often seek the advice of the attending physician. The child- and adolescent-specific questionnaire BEARS, which was developed by J. Owens and K. Mindell, allows the first diagnostic steps and classifications based on the most important symptoms such as bedtime problems, excessive daytime sleepiness, waking up at night, problems with regularity and sleep duration as well as nocturnal breathing disorders. The aim of this article is to show that important conclusions can be drawn in the everyday practice as to which symptoms need to be clarified how and how urgently, and which belong in the hands of a specialized sleep center.

The prevalence of inflammatory bowel disease (IBD) has increased over the past 20 years. Pulmonary involvement in paediatric IBD is rare but may be missed since the spectrum of symptoms is broad and mimics other diseases. The most important differential diagnoses of pulmonary manifestations of IBD are infections and therapy-related side-effects. There is no gold standard to diagnose respiratory manifestations in children with IBD. Diagnostic tests should be chosen according to history and clinical presentation. Treatment of respiratory manifestations of IBD includes inhaled or oral corticosteroids and initiation or step-up of immunomodulatory IBD therapies., Pulmonary involvement in paediatric IBD is rare but may be underdiagnosed. The spectrum of symptoms is broad and mimics other diseases. The differentiation between IBD-related and drug-induced pulmonary manifestation can be challenging. https://bit.ly/3uZBvpA

PICU hospitalization is particularly stressful for families. When it is prolonged and the prognostic is uncertain, it can significantly and negatively affect the whole family. To date, little is known on how families with a chronic critically ill (CCI) child are affected. This national study explored the specific PICU-related sources of stress, family functioning and needs of families of CCI patients during a PICU hospitalization. This descriptive qualitative study was conducted in the eight pediatric intensive care units in Switzerland. Thirty-one families with a child meeting the CCI criteria participated in semi-structured interviews. Interviews, including mothers only (n = 12), fathers only (n = 8), or mother and father dyads (n = 11), were conducted in German, French, or English by two trained researchers/clinical nurses specialists. Interviews were recorded, transcribed verbatim, and analyzed using deductive and inductive content analyses. Five overarching themes emerged: (1) high emotional intensity, (2) PICU-related sources of stress, (3) evolving family needs, (4) multi-faceted family functioning, and (5) implemented coping strategies. Our study highlighted the importance of caring for families with CCI children. Parents reported high negative emotional responses that affect their family functioning. Families experience was highly dependent on how HCPs were able to meet the parental needs, provide emotional support, reinforce parental empowerment, and allow high quality of care coordination.

We compared the impacts of linear (LP) and nonlinear (NLP) aerobic training periodizations on left ventricular (LV) function and geometry in coronary artery disease (CAD) patients. Thirty-nine CAD patients were randomized to either a 3-month isoenergetic supervised LP or NLP. All underwent standard echocardiography with assessment of 3D LV ejection fraction (LVEF), diastolic function, strain (global longitudinal, radial, and circumferential), and strain rate at baseline and study end. Training was performed 3 times/week and included high-intensity interval and moderate-intensity continuous training sessions. Training load was progressively increased in the LP group, while it was deeply increased and intercepted with a recovery week each fourth week in the NLP group. For the 34 analyzed patients, we found similar improvements for 3D LVEF (effect size (ES): LP, 0.29; NLP, 0.77), radial strain (ES: LP, 0.58; NLP, 0.48), and radial strain rate (ES: LP, 0.87; NLP, 0.17) in both groups (time for all: p ≤ 0.01). All other parameters of cardiac function remained similar. In conclusion, NLP and LP led to similar improvements in 3D LVEF and radial strain, suggesting a favourable positive cardiac remodelling through myofibers reorganization. These findings must be investigated in patients with more severe cardiac dysfunction. The study was registered on ClinicalTrials.gov (NCT03443193). Novelty: Linear and nonlinear periodization programs improved radial strain, accompanied by improvement of ejection fraction. Both aerobic periodization programs did not negatively impact cardiac function in coronary artery disease patients.

A lower heart rate (HR) during heat exposure is a classic marker of heat acclimation (HA), although it remains unclear whether this adaptation occurs secondary to reduced thermal strain and/or improvements in cardiac function. We evaluated the hypothesis that short-term passive HA reduces HR and improves cardiac function during passive heating. Echocardiography was performed under thermoneutral and hyperthermic conditions in 10 healthy adults (9 men/1 woman, 29 ± 6 yr old), pre and post 7 days of controlled hyperthermia. HR (P = 0.61), stroke volume (P = 0.99), and cardiac output (P = 0.99), were similar on days 1 and 7 of HA. Core (pre: 38.17 ± 0.42, post: 38.15 ± 0.27°C, P = 0.95) and mean skin (pre: 38.24 ± 0.41, post: 38.51 ± 0.29°C, P = 0.17) temperatures were similar during hyperthermic echocardiographic assessments. Cardiac systolic function was unaffected by HA (P ≥ 0.10). HA attenuated the decrease in end-diastolic volume (pre: -18 ± 18, post: -12 ± 19 mL, P = 0.05), accentuated the greater atrial contribution to diastolic filling (pre: +11 ± 5, post: +14 ± 5%, P = 0.02), and attenuated the increase in left atrial reservoir strain rate (pre: +1.5 ± 1.2, post: +0.8 ± 0.8 1/s, P = 0.02) during heating. Nonetheless, there were no differences in HR (pre: 106 ± 12, post: 104 ± 12 beats/min, P = 0.50), stroke volume (pre: 65 ± 15, post: 68 ± 13 mL, P = 0.55), or cardiac output (pre: 6.9 ± 2.0, post: 7.1 ± 1.7 L/min, P = 0.70) during passive heating. Short-term controlled hyperthermia HA results in limited adaptations of cardiac function during passive heating.NEW & NOTEWORTHY A lower heart rate during heat exposure is a classic marker of heat acclimation (HA). It remains unknown if improved cardiac function contributes to this response. A 7-day passive HA protocol did not alter cardiac systolic function during passive heating, whereas it improved some indexes of diastolic function in young adults. Nonetheless, heart rate during heating was unaffected by HA. These results suggest that passive HA induces limited adaptations in cardiac function during passive heating.

Background We aimed to compare: (1) two different periodized aerobic training protocols (linear (LP) versus non-linear (NLP)) on the cardiopulmonary exercise response in patients with coronary heart disease; (2) the proportion of responders between both training protocols. Design A randomized controlled trial. Methods A total of 39 coronary heart disease patients completed either LP ( n = 20, 65 ± 10 years) or NLP ( n = 19, 66 ± 5 years). All patients completed a cardiopulmonary exercise testing with gas exchange measurements. Patients underwent a 12-week supervised exercise program including an isoenergetic aerobic periodized training and a similar resistance training program, 3 times/week. Weekly energy expenditure was constantly increased in the LP group for the aerobic training, while it was deeply increased and intercepted with a recovery week each fourth week in the NLP group. Peak oxygen uptake (peak V̇O2), oxygen uptake efficiency slope, ventilatory efficiency slope (V̇E/V̇CO2 slope), V̇O2 at the first (VT1) and second (VT2) ventilatory thresholds, and oxygen pulse (O2 pulse) were measured. Responders were determined according the median value of the Δpeak V̇O2 (mL.min−1.kg−1). Results We found similar improvement for peak V̇O2 (LP: +8.1%, NLP: +5.3%, interaction: p = 0.37; time: p 1, VT2 and O2 pulse in both groups (interaction: p > 0.05; time: p Conclusion In contrast to the athletes, more variation (NLP) does not seem necessary for greater cardiopulmonary adaptations in coronary heart disease patients.

Background: 2,4,5-Trimethoxyamphetamine (TMA-2) is a potent psychedelic compound. Structurally related 4-alkyloxy-substituted 2,5-dimethoxyamphetamines and phenethylamine congeners (2C-O derivatives) have been described but their pharmacology is mostly undefined. Therefore, we examined receptor binding and activation profiles of these derivatives at monoamine receptors and transporters. Methods: Receptor binding affinities were determined at the serotonergic 5-HT1A, 5-HT2A, and 5-HT2C receptors, trace amine-associated receptor 1 (TAAR1), adrenergic α1 and α2 receptors, dopaminergic D2 receptor, and at monoamine transporters, using target-transfected cells. Additionally, activation of 5-HT2A and 5-HT2B receptors and TAAR1 was determined. Furthermore, we assessed monoamine transporter inhibition. Results: Both the phenethylamine and amphetamine derivatives (K i = 8–1700 nM and 61–4400 nM, respectively) bound with moderate to high affinities to the 5-HT2A receptor with preference over the 5-HT1A and 5-HT2C receptors (5-HT2A/5-HT1A = 1.4–333 and 5-HT2A/5-HT2C = 2.1–14, respectively). Extending the 4-alkoxy-group generally increased binding affinities at 5-HT2A and 5-HT2C receptors but showed mixed effects in terms of activation potency and efficacy at these receptors. Introduction of a terminal fluorine atom into the 4-ethoxy substituent by trend decreased, and with progressive fluorination increased affinities at the 5-HT2A and 5-HT2C receptors. Little or no effect was observed at the 5-HT1A receptor for any of the substances tested (K i ≥ 2700 nM). Phenethylamines bound more strongly to the TAAR1 (K i = 21–3300 nM) compared with their amphetamine analogs (K i = 630–3100 nM). Conclusion: As seen with earlier series investigated, the 4-alkyloxy-substituted 2,5-dimethoxyamphetamines and phenethylamines share some trends with the many other phenethylamine pharmacophore containing compounds, such as when increasing the size of the 4-substituent and increasing the lipophilicity, the affinities at the 5-HT2A/C subtype also increase, and only weak 5-HT2A/C subtype selectivities were achieved. At least from the binding data available (i.e., high affinity binding at the 5-HT2A receptor) one may predict mainly psychedelic-like effects in humans, at least for some of the compound investigated herein.

Introduction: Several diagnostic tests are used in children suspected for asthma, but the accuracy of these tests to diagnose asthma is unclear. Aim: We aimed to assess the diagnostic accuracy of reported respiratory symptoms and clinical tests to diagnose asthma in school-aged children under investigation for asthma. Methods: We studied cross-sectionally children aged 6-16 years referred to 2 pulmonary outpatient clinics with suspicion of asthma. All children underwent clinical evaluation including spirometry, fractional exhaled nitric oxide (FeNO), skin prick tests, and bronchial provocation tests (BPT) by exercise, methacholine, and mannitol. Symptoms were reported in a parental questionnaire. Asthma was diagnosed by the physicians based on medical history, clinical examination, and all clinical test results. We calculated sensitivity, specificity, positive and negative predictive value and area under the curve to assess the diagnostic accuracy of symptoms and clinical tests. Results: Of the 111 participants, 68 (61%) were diagnosed with asthma. The combined sensitivity and specificity to diagnose asthma was highest for wheeze without colds ((sensitivity/specificity) 0.76/0.65), wheeze (0.87/0.51), wheeze triggered by pollen (0.59/0.79) and more than 3 attacks of wheeze (0.49/0.88). Of the diagnostic tests, the area under the curve was highest for FeNO (0.81) and BPT by exercise (0.79) and lowest for FEV1 (0.52) and FEV1/FVC (0.58). Conclusion: This study, which needs validation in a larger sample, suggests that specific questions about triggers and severity of wheeze, FeNO and BPT by exercise are more useful to diagnose asthma in school-aged children than spirometry, skin prick tests and other BPTs.

Congenital lung anomalies are a group of rare malformations, often diagnosed during the prenatal period. Guidelines on how to manage these patients are currently under debate, especially with regard to prophylactic surgery in asymptomatic patients, or how to proceed with conservative follow-up. Currently, there is no clear consensus on management strategies. A Swiss congenital lung anomaly national database and biobank was created in 2016 to enable data recording and collection of surgical lung samples in order to help define the most appropriate management strategies. This national observational cohort study represents an important step towards a better understanding of the pathophysiology and clinical course of the diseases included under congenital lung anomalies, especially in the context of a small country like Switzerland.

INTRODUCTION The contribution of clinical investigations to prediction of long-term outcomes of children investigated for asthma is unclear. AIM We performed a broad range of clinical tests and investigated whether they helped to predict long-term wheeze among children referred for evaluation of possible asthma. METHODS We studied children aged 6 to 16 years referred to two Swiss pulmonary outpatient clinics with a history of wheeze, dyspnea, or cough in 2007. The initial assessment included spirometry, fractional exhaled nitric oxide, skin prick tests, and bronchial provocation tests by exercise, methacholine, and mannitol. Respiratory symptoms were assessed with questionnaires at baseline and at follow-up 7 years later. Associations between baseline factors and wheeze at follow-up were investigated by logistic regression. RESULTS At baseline, 111 children were examined in 2007. After 7 years, 85 (77%) completed the follow-up questionnaire, among whom 61 (72%) had wheeze at baseline, while at follow-up 39 (46%) reported wheeze. Adjusting for age and sex, the following characteristics predicted wheeze at adolescence: wheeze triggered by pets (odds ratio, 4.2; 95% CI, 1.2-14.8), pollen (2.8, 1.1-7.0), and exercise (3.1, 1.2-8.0). Of the clinical tests, only a positive exercise test (3.2, 1.1-9.7) predicted wheeze at adolescence. CONCLUSION Reported exercise-induced wheeze and wheeze triggered by pets or pollen were important predictors of wheeze persistence into adolescence. None of the clinical tests predicted wheeze more strongly than reported symptoms. Clinical tests might be important for asthma diagnosis but medical history is more helpful in predicting prognosis in children referred for asthma.

Rationale: Damage control is a staged surgical approach to manage polytraumatized patients. The damage control approach comprises three steps. First, bleeding is controlled and fractures are stabilized temporarily; second, vital parameters are stabilized and the child is rewarmed in the intensive care unit; and third, the child is reoperated for definitive repair of injuries. We aimed to describe the feasibility of the damage control orthopedic approach in a child. Patient concerns: An 8-year-old girl fell from the balcony of the 5th floor onto concrete pavement and was admitted to our accident and emergency ward in a stable cardiorespiratory state, but with gross deformity of the lower limbs, left thigh, and forearm. Diagnoses: The child had sustained multiple injuries with severe bilateral lung contusion, pneumothorax, fracture of first rib, liver laceration, stable spine fractures, transforaminal fracture of sacrum, pelvic ring fracture, displaced baso-cervical femoral neck fracture, displaced bilateral multifragmental growth plate fractures of both tibiae, fractures of both fibulae, displaced fracture of left forearm, and displaced supracondylar fracture of the humerus. Intervention: In the initial operation, we performed closed reduction and K-wire fixation of the right tibia, closed reduction and external fixation of the left tibia, open reduction and screw osteosynthesis of the femoral neck fracture, closed reduction and K-wire fixation of the radius, and closed reduction of the supracondylar fracture. Subsequently, we transferred the girl to the pediatric intensive care unit for hemodynamic stabilization, respiratory therapy, rewarming, and treatment of crush syndrome. In a third step, 10 days after the injury, we managed the supracondylar fracture of the humerus by closed reduction and K-wire fixation. Outcomes: Growth arrest of the left distal tibial growth plate and osteonecrosis of the femoral head and neck, slipped capital femoris epiphysis (SCFE), and coxa vara of the right femur led to balanced leg length inequality 2 years after the injury. The lesion of the left sciatic nerve improved over time and the girl walked without walking aids and took part in school sports but avoided jumping exercises. Lessons: We emphasize the importance of damage control principles when managing polytraumatized children.

An 8-year-old girl developed severe acute lung injury after irrigation of a pelvic aneurysmal bone cyst with H2O2 and filling with bone cement. Sudden profound oxygen desaturation occurred on the operating table when the patient was turned from the prone to the supine position. After a brief improvement in her oxygenation, the girl developed rapidly progressing severe respiratory failure necessitating reintubation and hour-long manual ventilation, while copious amounts of hemorrhagic frothy fluids were aspirated through the endotracheal tube. The patient started to improve after 24 hours and eventually made a full recovery. We hypothesize that the incident was caused by gas embolization and pulmonary endothelial damage by H2O2.

Respiratory adverse events are one of the major causes of morbidity and mortality in paediatric anaesthesia. Aside from predisposing conditions associated with an increased risk of respiratory incidents in children such as concurrent infections and chronic airway irritation, there are adverse respiratory events directly attributable to the impact of anaesthesia on the respiratory system. Anaesthesia can negatively affect respiratory drive, ventilation/perfusion (V/Q) matching and tidal breathing, all resulting in potentially devastating hypoxaemia. Understanding paediatric respiratory physiology and its changes during anaesthesia will enable anaesthetists to anticipate, recognize and prevent deterioration that can lead to respiratory failure. This review aims to give a comprehensive overview of the effects of anaesthesia on respiration in children. It focuses on the impact of the different components of anaesthesia, patient positioning and procedure-related changes on respiratory physiology.

Background: In PE patients, treatment often leads to subjective improvements of exercise capacity and dyspnoea. Objective changes in lung function, in contrast, are often lacking. We hypothesized that respiratory system reactance (Xrs) assessed at high lung volumes by the forced oscillation technique (FOT) would be more sensitive than conventional lung function tests to the respiratory pathophysiology of PE. Our aim was to investigate if, in PE patients treated by non-surgical vacuum bell therapy, longitudinal changes in Xrs are related to changes in chest wall deformity. Methods: 31 PE patients (mean(SD) age=13(3) years) underwent FOT at 5 Hz, spirometry and body plethysmography at 3-6 months intervals for the duration of the treatment. FOT was performed during spontaneous breathing followed by a slow vital capacity manoeuvre. Xrs was evaluated during tidal inspiration and expiration (XINSP, XEXP) and at TLC (XTLC). The association between lung function and chest wall deformity was assessed by multilevel linear regression and adjusted for height and weight if appropriate. Results: At baseline, patients had a mean(95%CI) FEV1 = 93(87,98)%pred, FEV1/FVC = 89(87,90)%, RV/TLC = 29(26,31)%, TLC = 94(89,98)%pred, XINSP = -1.2(-1.5,-0.9) cmH2O*s/L, XEXP = -1.4(-1.7,-1.0) cmH2O*s/L and XTLC = -2.2(-2.6,-1.8) cmH2O*s/L. FEV1 and FEV1/FVC presented a weak but significant decrease over time. Within each patient, depth of deformity was significantly associated with XTLC (p=0.001, R2=0.21) but not with either XINSP, XEXP, spirometric or plethysmografic parameters. Conclusion: Our results suggest that chest wall deformity may be associated with reduced chest wall compliance detected by FOT only at higher lung volumes.

BACKGROUND Laryngeal clefts (LC) are uncommon but important causes of stridor in infants. Direct laryngoscopy is the recommended method for the detection of LC because LC may be missed by flexible endoscopy. As laryngomalacia by far outnumbers any other cause of stridor in this age group flexible bronchoscopy is usually the preferred method for the evaluation of significant infantile stridor. The aim is to illustrate how the application of CPAP assists the detection of LC during flexible endoscopy. METHOD Continuous positive airway pressure (CPAP) is applied via endoscopy mask during flexible endoscopy, titrated to open the upper esophageal sphincter, and to spread the inter-arytenoid folds. RESULTS The application of CPAP of 10-15 cmH2 O resulted in visual unmasking of otherwise obscured LC in four young children assessed for congenital stridor. CONCLUSION CPAP helps visualize LC by flexible endoscopy obviating transition to direct laryngoscopy and manual exploration.

BACKGROUND Lung clearance index (LCI), a marker of ventilation inhomogeneity, is elevated early in children with cystic fibrosis (CF). However, in infants with CF, LCI values are found to be normal, although structural lung abnormalities are often detectable. We hypothesized that this discrepancy is due to inadequate algorithms of the available software package. AIM Our aim was to challenge the validity of these software algorithms. METHODS We compared multiple breath washout (MBW) results of current software algorithms (automatic modus) to refined algorithms (manual modus) in 17 asymptomatic infants with CF, and 24 matched healthy term-born infants. The main difference between these two analysis methods lies in the calculation of the molar mass differences that the system uses to define the completion of the measurement. RESULTS In infants with CF the refined manual modus revealed clearly elevated LCI above 9 in 8 out of 35 measurements (23%), all showing LCI values below 8.3 using the automatic modus (paired t-test comparing the means, P

Regelmässiges körperliches Training induziert strukturelle, elektrische und funktionelle Anpassungen des Herzens. Die grösste Herausforderung für den Arzt liegt darin, Veränderungen hinweisend für eine strukturelle Herzerkrankung von physiologischen, trainingsassoziierten Anpassungen im Sinne eines 'Athlete's heart' zu unterscheiden. Bei zugrundliegender Kardiopathie ist sportliche Aktivität nicht die Ursache, sondern kann ein Trigger für belastungsabhängige Tachyarrhythmien bzw. für den belastungsabhängigen plötzlichen Herztod (SCD) sein. Um Athleten mit einer kardialen Grunderkrankung und erhöhtem Risiko für einen SCD frühzeitig zu identifizieren wird in Europa ein Preparticipation Screening empfohlen, welches von der Schweizerischen Gesellschaft für Sportmedizin (SGSM) übernommen wurde. Dieses Screening umfasst neben der spezifischen Anamnese und der Herzauskultation auch ein Ruhe-Elektrokardiogramm (Ruhe-EKG). Aufgrund der hohen Anzahl falsch-positiver EKG-Befunde wurden in den letzten Jahren die Beurteilungskriterien des Athleten-EKGs wiederholt angepasst, die Sensitivität und insbesondere auch die Spezifität konnte mit den „verfeinerten Seattle Kriterien“ 2014 deutlich verbessert werden. Der frühen Repolarisation galt in den letzten Jahren ein Hauptaugenmerk: neben dem (Ausdauer-) Training besteht eine klare Assoziation zum männlichen Geschlecht, zur Ethnie, zu den Veränderungen des vegetativen Nervensystems und zu erhöhten QRS-Voltage-Kriterien.

Objectives Standard inflammatory markers and chest radiography lack the ability to discriminate bacterial from non-bacterial lower respiratory tract infection (LRTI). Cytokine profiles may serve as biomarkers for LRTI, but their applicability to identify aetiology, severity of disease and need for antibiotic prescription in children remains poorly defined. Objectives were to determine the cytokine kinetic profiles over 5 days in paediatric patients with LRTI, to investigate the relationship between cytokine patterns, and clinical and laboratory variables. Methods We included patients aged 1 month to 18 years, with febrile LRTI and three consecutive cytokines measurements on days 1, 3 and 5 of a randomized controlled trial (ProPAED study). We evaluated differences in cytokine concentrations between days and associations with clinical and laboratory variables. Results A total of 181 patients (median age 4.1 years) were included; 72/181 (40%) received antibiotics. Serum concentrations of interferon (IFN)-γ, interleukin (IL)-1ra, IL-6, IL-10, IFN-γ-inducible protein (IP)-10 and tumor necrosis factor-α were elevated on day 1 and decreased subsequently, with the greatest decline between day 1 and 3 (by −8 to >−94%). Procalcitonin (PCT) and C-reactive protein (CRP) values showed a protracted decrease with the most prominent reduction in concentrations between days 3 and 5. Significantly elevated IL-6 concentrations were associated with hospital admission, antibiotic treatment, and prolonged antibiotic treatment. Bacteraemic LRTI patients had higher concentrations of IL-1ra (p Conclusions We observed an earlier decrease of elevated cytokines compared to PCT or CRP. Both pro- and anti-inflammatory cytokines may serve as markers for severity of LRTI.

Pulmonary artery sling is a rare congenital condition in which the left pulmonary artery (LPA) arises from the right pulmonary artery, and then passes between the trachea and the esophagus to reach the left lung, thereby forming a sling around the airway. It is often associated with intrinsic tracheal stenosis due to complete cartilaginous rings. Therapeutic management nowadays consists of one-stage reimplantation of the LPA and tracheoplasty with cardiopulmonary bypass support. Here we present a 7-weeks-old boy with pulmonary artery sling and long-segment distal tracheal stenosis who underwent surgical intervention consisting of reimplantation of the LPA and slide tracheoplasty. Multiple respiratory and cardiovascular complications marked the postoperative course. They consisted of recurrent failed attempts in weaning off mechanical ventilation due to bronchomalacia, left vocal cord paralysis, development of granulation tissue at the anastomosis and restenosis of the trachea and the main stem bronchi requiring balloon dilatation. The patient also developed bilateral pulmonary artery thrombosis and stenosis of the LPA. After a prolonged hospitalization, the patient is doing well without any respiratory symptoms and has a good result on follow-up bronchoscopy 1 year after the initial surgery. The stenosis of the LPA responded well to percutaneous balloon dilatation 12 months after the primary surgery. The case illustrates that even though surgical techniques are improving and are in general associated with a low morbidity and mortality, management of pulmonary artery sling and tracheal stenosis can still be challenging. However, good long-term outcome can be achieved if the initial postoperative phase is overcome.

Background 4-Thio-substituted phenethylamines (2C-T drugs) are potent psychedelics with poorly defined pharmacological properties. Because of their psychedelic effects, 2C-T drugs are sometimes sold as new psychoactive substances (NPSs). The aim of the present study was to characterize the monoamine receptor and transporter interaction profiles of a series of 2C-T drugs. Methods We determined the binding affinities of 2C-T drugs at monoamine receptors and transporters in human cells that were transfected with the respective receptors or transporters. We also investigated the functional activation of serotonergic 5-hydroxytryptamine 2A (5-HT2A) and 5-HT2B receptors, activation of human trace amine-associated receptor 1 (TAAR1), and inhibition of monoamine uptake transporters. Results 2C-T drugs had high affinity for 5-HT2A and 5-HT2C receptors (1–54 nM and 40–350 nM, respectively). With activation potencies of 1–53 nM and 44–370 nM, the drugs were potent 5-HT2A receptor and 5-HT2B receptor, respectively, partial agonists. An exception to this were the benzylthiophenethylamines, which did not potently activate the 5-HT2B receptor (EC50 > 3000 nM). Furthermore, the compounds bound to serotonergic 5-HT1A and adrenergic receptors. The compounds had high affinity for the rat TAAR1 (5–68 nM) and interacted with the mouse but not human TAAR1. The 2C-T drugs did not potently interact with monoamine transporters (Ki > 4000 nM). Conclusion The receptor binding profile of 2C-T drugs predicts psychedelic effects that are mediated by potent 5-HT2 receptor interactions. This article is part of the Special Issue entitled ‘Designer Drugs and Legal Highs.’

IntroductionThere are few data on the usefulness of different tests to diagnose asthma in children.AimWe assessed the contribution of a detailed history and a variety of diagnostic tests for diagnosing asthma in children.MethodsWe studied children aged 6–16 years referred consecutively for evaluation of suspected asthma to two pulmonary outpatient clinics. Symptoms were assessed by parental questionnaire. The clinical evaluation included skin-prick tests, measurement of exhaled nitric oxide fraction (FeNO), spirometry, bronchodilator reversibility and bronchial provocation tests (BPT) by exercise, methacholine and mannitol. Asthma was diagnosed by the physicians at the end of the visit. We assessed diagnostic accuracy of symptoms and tests by calculating sensitivity, specificity, positive and negative predictive values and area under the curve (AUC).ResultsOf the 111 participants, 80 (72%) were diagnosed with asthma. The combined sensitivity and specificity was highest for reported frequent wheeze (more than three attacks per year) (sensitivity 0.44, specificity 0.90), awakening due to wheeze (0.41, 0.90) and wheeze triggered by pollen (0.46, 0.83) or by pets (0.29, 0.99). Of the diagnostic tests, the AUC was highest forFeNOmeasurement (0.80) and BPT by methacholine (0.81) or exercise (0.74), and lowest for forced expiratory volume in 1 s (FEV1) (0.62) and FEV1/forced vital capacity ratio (0.66), assessed by spirometry.ConclusionThis study suggests that specific questions about triggers and severity of wheeze, measurement ofFeNOand BPT by methacholine or exercise contribute more to the diagnosis of asthma in school-aged children than spirometry, bronchodilator reversibility and skin-prick tests.

Background Topical lidocaine has been found to result in overestimation of the severity of laryngomalacia in infants undergoing flexible bronchoscopy under conscious sedation with midazolam and nalbuphine. This effect has never been confirmed and may depend on the level of sedation and the drugs used. We assessed the effect of topical lidocaine on laryngomalacia in infants undergoing flexible bronchoscopy under general anesthesia with propofol. Methods Thirteen infants with congenital stridor referred to diagnostic flexible video-bronchoscopy were studied under propofol anesthesia before and 3 minutes after topical lidocaine administration to the larynx at a dose of 3 mg/kg body weight. Laryngomalacia was scored using 60 seconds video recordings of the larynx before and after lidocaine administration in random order by 2 independent blinded observers using the previously described arytenoid score (AS), epiglottis score (ES), and the total score (TS=AS+ES). Results No significant differences in AS, ES, and laryngomalacia score were found between the prelidocaine and postlidocaine assessments by the 2 raters. The intraclass correlation coefficients were 0.995 (95% confidence interval, 0.986-0.998) and 0.975 (0.930-0.991) and 0.989 (0.971-996) for AS, ES, and TS, respectively. Conclusions The assessment of laryngomalacia is not affected by topical lidocaine under propofol anesthesia. The lidocaine effect on laryngomalacia may vary depending on the medication regime used and the depth of procedural sedation.

The so-called psychedelic phenethylamines represent a class of drugs with a large range of psychoactive properties in humans, ranging from naturally occurring mescaline to amphetamine analogues and homologues. The interest in many of these compounds, occasionally referred to as designer-drugs, is widely dispersed across popular culture and political and scientific communities. In recent decades, fluorine has become a powerful and important tool in medicinal chemistry. In addition, fluorine-containing compounds and medicines can be found in numerous commercially successful pharmaceuticals that have gained a market share of some 5–15%. One might anticipate this trend to increase in the future. As far as fluorinated phenethylamines are concerned, much less is known about their chemistry and pharmacology. This paper provides an overview regarding the biological properties of over 60 fluorinated phenethylamines and discusses both historical and recent chemistry-related developments. It was shown that the introduction of fluorine into the phenethylamine nucleus can impact greatly on psychoactivity of these compounds, ranging from marked loss to enhancement and prolongation of effects. For example, in contrast to the psychoactive escaline (70), it was observed that its fluoroescaline (76) counterpart was almost devoid of psychoactive effects. Difluoroescaline (77), on the other hand, retained, and trifluoroescaline (78) showed increased human potency of escaline (70). Difluoromescaline (72) and trifluoromescaline (73) increasingly surpassed human potency and duration of mescaline (22) effects. Copyright © 2012 John Wiley & Sons, Ltd.

Exercise is an important aspect of health and development in children. By placing the pulmonary system under stress, exercise testing may reveal subtle dynamic abnormalities that are not apparent on conventional static pulmonary function tests. Furthermore, exercise testing assesses the functional impact of respiratory disease on children. Exercise testing has been used in children with a variety of respiratory diseases such as exercise induced bronchoconstriction, asthma, cystic fibrosis and bronchopulmonary dysplasia to assess the severity of disease as well as response to various interventions. Furthermore, there is good evidence that exercise testing is a useful tool to help determine prognosis in patients with cystic fibrosis. In addition to the clinical utility, exercise testing is also becoming an increasingly important outcome measure in research studies.

Acute bronchiolitis is the most common lower respiratory tract infection in infants and there is no evidence that drug treatment alters its natural course. Despite this, most Swiss paediatricians reported in 2001 prescribing bronchodilators and inhaled corticosteroids (ICS). This situation led to the creation of national guidelines followed by a tailored implementation programme. The aim of this study was to examine if treatment practices changed after the implementation of the new guidelines.A questionnaire on treatment of bronchiolitis was sent to all Swiss paediatricians before (2001) and after (2006) creation and implementation of national guidelines (2003-2005). Guidelines were created in collaboration with all paediatric pulmonologists and implemented carefully using a multifaceted approach.Questionnaires were returned by 541 paediatricians (58%) in 2001 and by 639 (54%) in 2006. While both surveys showed a wide variation in the treatment of bronchiolitis between physicians, reported drug prescription decreased significantly between the two surveys. For outpatients, general use (for all patients) of bronchodilators dropped from 60% to 23%, and general use of ICS from 34% to 6%. For inpatients, general use of bronchodilators and ICS dropped from 55% to 18% and from 26% to 6%, respectively (all p0.001). The decrease was evident in all regions, among hospital and primary care physicians, and among general paediatricians and paediatric pulmonologists.National guidelines together with a tailored implementation programme can have a major impact on medical management practices in a country.

Background Ivacaftor acts as a potentiator of the cystic fibrosis transmembrane conductance regulator (CFTR) and increases the transepithelial chloride transport of CFTR in 9 of 10 known gating mutations causing cystic fibrosis. S549R is a rare gating mutation considered to be less sensitive to potentiators than all other gating mutations. Case presentation We report our first experience with ivacaftor in an 8-year-old boy with the rare S549R gating mutation. Besides subjective clinical improvements, the sweat chloride level and the lung clearance index decreased impressively within a few weeks of treatment while forced expiratory volume in the first second values remained in normal range. Conclusion We emphasize the value of measuring small airway function by lung clearance index as an outcome measure for new interventions targeting the correction of the CFTR defect at an age before traditional lung function parameters start to deteriorate.