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Background: Volumetric capnography allows for continuous monitoring of expired tidal volume and carbon dioxide. The slope of the alveolar plateau of the capnogram (S III ) could provide information regarding ventilation homogeneity. We aimed to assess the feasibility of measuring S III during newborn resuscitation and determine if S III decreased after surfactant indicating ventilation inhomogeneity improvement., Methods: Respiratory function traces of preterm infants resuscitated at birth were analysed. Ten capnograms were constructed for each infant: five pre- and post-surfactant. If a plateau was present S III was calculated by regression analysis., Results: Thirty-six infants were included, median gestational age of 28.7 weeks and birth weight of 1055 g. Average time between pre- and post-surfactant was 3.2 min. Three hundred and sixty capnograms (180 pre and post) were evaluated. There was adequate slope in 134 (74.4%) capnograms pre and in 100 (55.6%) capnograms post-surfactant (p = 0.004). Normalised for tidal volume S III pre-surfactant was 18.89 mmHg and post-surfactant was 24.86 mmHg (p = 0.006). An increase in S III produced an up-slanting appearance to the plateau indicating regional obstruction., Conclusion: It was feasible to evaluate the alveolar plateau pre-surfactant in preterm infants. Ventilation inhomogeneity increased post-surfactant likely due to airway obstruction caused by liquid surfactant present in the airways., Impact: Volumetric capnography can be used to assess homogeneity of ventilation by S III analysis. Ventilation inhomogeneity increased immediately post-surfactant administration during the resuscitation of preterm infants, producing a characteristic up-slanting appearance to the alveolar plateau. The best determinant of alveolar plateau presence in preterm infants was the expired tidal volume., (© 2021. The Author(s).)

Background: Many preterm infants require supplemental oxygen in the newborn period but experience frequent fluctuations of their oxygen saturation levels. Intermittent episodes of hypoxia or hyperoxia increase the risk of complications. Compliance with achievement of oxygen saturation targets is variable, and the need for frequent adjustments of the inspired oxygen concentration increases workload. Closed-loop automated oxygen control systems (CLAC) improve achievement of oxygen saturation targets and reduce both episodes of hypoxia and hyperoxia and the number of manual adjustments. This study investigates whether CLAC compared with manual oxygen control reduces the duration of mechanical ventilation in preterm infants born at less than 31 weeks of gestation., Methods: This randomised controlled trial performed at a single tertiary neonatal unit is recruiting 70 infants born at less than 31 weeks of gestational age and within 48 h of initiation of mechanical ventilation. Infants are randomised to CLAC or manual oxygen control from recruitment until successful extubation. The primary outcome is the duration of mechanical ventilation, and secondary outcomes are the percentage of time spent within target oxygen saturation ranges, the time spent in hypoxia or hyperoxia, the number of manual adjustments required, the number of days on oxygen, the incidence of bronchopulmonary dysplasia and the length and cost of neonatal unit stay. The study is performed following informed parental consent and was approved by the Yorkshire and the Humber-Sheffield Research Ethics Committee (protocol version 1.1, 13 July 2021)., Discussion: This trial will investigate the effect of CLAC on the duration of mechanical ventilation, which is an important clinical outcome as prolonged mechanical ventilation is associated with important adverse outcomes, such as bronchopulmonary dysplasia., Trial Registration: ClinicalTrials.Gov NCT05030337 . Registered on 17 August 2021., (© 2022. The Author(s).)

Our aim was to summarise the current evidence and methods used to assess respiratory muscle function in the newborn, focusing on current and future potential clinical applications. The respiratory muscles undertake the work of breathing and consist mainly of the diaphragm, which in the newborn is prone to dysfunction due to lower muscle mass, flattened shape and decreased content of fatigue-resistant muscle fibres. Premature infants are prone to diaphragmatic dysfunction due to limited reserves and limited capacity to generate force and avoid fatigue. Methods to assess the respiratory muscles in the newborn include electromyography, maximal respiratory pressures, assessment for thoraco-abdominal asynchrony and composite indices, such as the pressure-time product and the tension time index. Recently, there has been significant interest and a growing body of research in assessing respiratory muscle function using bedside ultrasonography. Neurally adjusted ventilator assist is a novel ventilation mode, where the level of the respiratory support is determined by the diaphragmatic electrical activity. Prolonged mechanical ventilation, hypercapnia and hypoxia, congenital anomalies and systemic or respiratory infection can negatively impact respiratory muscle function in the newborn, while caffeine and synchronised or volume-targeted ventilation have a positive effect on respiratory muscle function compared to conventional, non-triggered or pressure-limited ventilation, respectively. IMPACT: Respiratory muscle function is impaired in prematurely born neonates and infants with congenital anomalies, such as congenital diaphragmatic hernia. Respiratory muscle function is negatively affected by prolonged ventilation and infection and positively affected by caffeine and synchronised compared to non-synchronised ventilation modes. Point-of-care diaphragmatic ultrasound and neurally adjusted ventilator assist are recent diagnostic and therapeutic technological developments with significant clinical applicability., (© 2021. The Author(s).)

Background: Dead space is the volume not taking part in gas exchange and, if increased, could affect alveolar ventilation if there is too low a delivered volume. We determined if there were differences in dead space and alveolar ventilation in ventilated infants with pulmonary disease or no respiratory morbidity., Methods: A prospective study of mechanically ventilated infants was undertaken. Expiratory tidal volume and carbon dioxide levels were measured. Volumetric capnograms were constructed to calculate the dead space using the modified Bohr-Enghoff equation. Alveolar ventilation (V A ) was also calculated., Results: Eighty-one infants with a median (range) gestational age of 28.7 (22.4-41.9) weeks were recruited. The dead space [median (IQR)] was higher in 35 infants with respiratory distress syndrome (RDS) [5.7 (5.1-7.0) ml/kg] and in 26 infants with bronchopulmonary dysplasia (BPD) [6.4 (5.1-7.5) ml/kg] than in 20 term controls with no respiratory disease [3.5 (2.8-4.2) ml/kg, p < 0.001]. Minute ventilation was higher in both infants with RDS or BPD compared to the controls. V A in infants with RDS or BPD was similar to that of the controls [p = 0.54]., Conclusion: Prematurely born infants with pulmonary disease have a higher dead space than term controls, which may influence the optimum level during volume-targeted ventilation., Impact: Measurement of the dead space was feasible in ventilated newborn infants. The physiological dead space was a significant proportion of the delivered volume in ventilated infants. The dead space (per kilogram) was higher in ventilated infants with respiratory distress syndrome or evolving bronchopulmonary dysplasia compared to term controls without respiratory disease. The dead space volume should be considered when calculating the most appropriate volume during volume-targeted ventilation., (© 2021. The Author(s).)

Objective: To assess whether end-tidal capnography (EtCO 2 ) monitoring reduced the magnitude of difference in carbon dioxide (CO 2 ) levels and the number of blood gases in ventilated infants., Study Design: A case-control study of a prospective cohort (n = 36) with capnography monitoring and matched historical controls (n = 36)., Result: The infants had a median gestational age of 31.6 weeks. A reduction in the highest CO 2 level on day 1 after birth was observed after the introduction of EtCO 2 monitoring (p = 0.043). There was also a reduction in the magnitude of difference in CO 2 levels on days 1 (p = 0.002) and 4 (p = 0.049) after birth. There was no significant difference in the number of blood gases., Conclusion: Continuous end-tidal capnography monitoring in ventilated infants was associated with a reduction in the degree of the magnitude of difference in CO 2 levels and highest level of CO 2 on the first day after birth., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc. part of Springer Nature.)

Background: Patent Ductus Arteriosus (PDA) is a common condition, affecting nearly half of infants born before 28 weeks' of gestation, and it has been associated with poor growth. It is not known if different treatment modalities are associated with more profound growth impairment. Our aim was to compare differences in weight gain at 36 weeks' corrected gestational age (CGA) in premature infants that received medical, surgical or conservative management for PDA., Methods: We retrospectively reviewed notes of 208 infants born under 30 weeks' gestation with a diagnosis of PDA. Gestational age (GA) at birth, birth weight z-score, CGA and weight z-score at 36 weeks' CGA were collected. In our cohort, surgical closure was performed in infants who remained symptomatic after medical or conservative management., Results: Ninety-four infants had medical, 56 surgical and 58 conservative management. Surgically managed infants had a lower median (IQR) GA [24.4 (24.0-26.1) weeks'] than medically [25.4 (24.6-26.5) weeks'] or conservatively managed [26.4 (25.4-28.1) weeks', p < 0.001] infants. There was no difference in birth weight z-scores across the groups. Surgically managed infants demonstrated a greater decrease in weight z-score [-2.24 (-2.89 to -1.53)] compared to medically [-1.79 (-2.45 to -1.35)] and conservatively [-1.57 (-1.99 to -1.28), p < 0.001] managed infants between birth and 36 weeks' CGA. After adjusting for GA at birth, definitive treatment modality was significantly related to change in weight z-score from birth to 36 weeks' CGA (adjusted p = 0.022)., Conclusion: Premature infants with PDA who were managed surgically had a greater degree of faltering growth compared to those who were treated medically or conservatively., Competing Interests: Declaration of Competing Interest No conflicts of interest to declare., (Copyright © 2020. Published by Elsevier B.V.)

Both proportional assist ventilation (PAV) and neurally adjusted ventilatory assist (NAVA) provide pressure support synchronised throughout the respiratory cycle proportional to the patient's respiratory demand. Our aim was to compare the effect of these two modes on oxygenation in infants with evolving or established bronchopulmonary dysplasia. Two-hour periods of PAV and NAVA were delivered in random order to 18 infants born less than 32 weeks of gestation. Quasi oxygenation indices ("OI") and alveolar-arterial ("A-a") oxygen gradients at the end of each period on PAV, NAVA and baseline ventilation were calculated using capillary blood samples. The mean "OI" was not significantly different on PAV compared to NAVA (7.8 (standard deviation (SD) 3.2) versus 8.1 (SD 3.4), respectively, p = 0.70, but lower on both than on baseline ventilation (mean baseline "OI" 11.0 (SD 5.0)), p = 0.002, 0.004, respectively). The "A-a" oxygen gradient was higher on PAV and baseline ventilation than on NAVA (20.8 (SD 12.3) and 22.9 (SD 11.8) versus 18.5 (SD 10.8) kPa, p = 0.015, < 0.001, respectively).Conclusion: Both NAVA and PAV improved oxygenation compared to conventional ventilation. There was no significant difference in the mean "OI" between the two modes, but the mean "A-a" gradient was better on NAVA.What is Known:• Proportional assist ventilation (PAV) and neurally adjusted ventilatory assist (NAVA) can improve the oxygenation index (OI) in prematurely born infants.• Both PAV and NAVA can provide support proportional to respiratory drive or demand throughout the respiratory cycle.What is New:• In infants with evolving or established BPD, using capillary blood samples, both PAV and NAVA compared to baseline ventilation resulted in improvement in the "OI", but there was no significant difference in the "OI" on PAV compared to NAVA.• The "alveolar-arterial" oxygen gradient was better on NAVA compared to PAV.

Background: Infants born preterm are at increased risk of pulmonary morbidity. The contribution of antenatal factors to impairments in lung structure/function has not been fully elucidated. This study aimed to compare standardized lung volumes from foetuses that were delivered <32 weeks' gestation with foetuses that were delivered >37 weeks., Methods: Fourteen women who delivered <32 weeks gestation and 56 women who delivered >37 underwent a foetal MRI. Slice-volume reconstruction was then used and the foetal lungs were then segmented using multi-atlas approaches. Body volumes were calculated by manual segmentation and lung:body volume ratios generated., Results: Mean gestation at MRI of the preterm group was 27 +2 weeks (SD 2.9, range 20 +6 -31 +3 ) and control group 25 +3 weeks (SD 4.7 range 20 +5 -31 +6 ). Mean gestation at delivery of the preterm group was 29 +2 weeks (SD 2.6, range 22 +0 -32 +0 ). Lung:body volume ratios and foetal lung volumes were smaller in foetuses that were delivered preterm both with and without preterm premature rupture of membranes compared to those born at term (p < 0.001 in all cases)., Conclusions: Foetuses that were delivered very preterm had reduced lung volumes when standardized for foetal size, irrespective of ruptured membranes. These are novel findings and suggest an antenatal aetiology of insult and possible focus for future preventative therapies.

Background: Administration of caffeine citrate can facilitate extubation. Our aim was to determine whether a loading dose of caffeine citrate given to ventilated, preterm infants affected the diaphragm electrical activity., Methods: Infants <34 weeks of gestational age were recruited if requiring mechanical ventilation and prescribed a loading dose of caffeine citrate. Surface electrodes recorded the electrical activity of the diaphragm (dEMG) before and after administration of intravenous caffeine citrate. The mean amplitude of the EMG (dEMG) trace and the mean area under the EMG curve (aEMGc) were calculated., Results: Thirty-two infants were assessed with a median gestational age of 29 (27-31) weeks. The dEMG amplitude increased, peaking at 25 min post administration (p = 0.006), and the increase in aEMGc (p = 0.004) peaked at 30 min; the differences were not significant after 60 min. At 20 min, there was an increase in minute volume (p = 0.034) and a reduction in the peak inspiratory pressure (p = 0.049)., Conclusions: We have demonstrated a transient increase in both electrical activity of the diaphragm and respiratory function following an intravenous loading dose of caffeine citrate.

Background: Nutrition is closely related to mortality and pulmonary and respiratory muscle function in cystic fibrosis (CF) patients. We initially validated results from a bioelectrical impedance device against dual energy x-ray absorptiometry (DEXA). We then determined whether fat free mass assessed by a portable impedance device rather than body mass index (BMI) better correlated with pulmonary function, respiratory muscle strength and exercise capacity in CF patients., Methods: Eighteen young people and adults (median age 19, range 12-39 years) with CF had dual energy X-ray absorptiometry and direct segmental multi-frequency impedance analysis. Body composition, pulmonary function, respiratory muscle function and exercise tolerance using the impedance device were measured in 29 young people with CF with median age 15 (range 12-19) years., Main Findings: There was a significant correlation between impedance and absorptiometry results (r 2  = 0.947). Fat free mass correlated with the forced vital capacity z-score (r = 0.442, p = 0.016), maximal inspiratory pressure (r = 0.451, p = 0.014) and exercise tolerance (r = 0. 707, p < 0.001). BMI z-scores did not significantly correlate with pulmonary or respiratory muscle function. Subjects with a fat free mass z-score of ≤2 had a lower forced expiratory volume in 1 s z-score (p = 0.007), lower forced vital capacity z-score (p = 0.001), higher residual volume z-score (p = 0.042), lower maximal inspiratory pressure (p = 0.039), more days of intravenous antibiotics per year (p = 0.016) and a higher rate of chronic infections (p = 0.006)., Principal Conclusions: Fat-free mass measured by impedance correlated better with pulmonary and respiratory muscle function and exercise capacity than BMI., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Pulmonary dead space (V D ) is an index of ventilation inhomogeneity and one of the determinants of the magnitude of tidal volume to maintain optimal blood gases., Aims: To identify the determinants of V D in ventilated newborns and to investigate differences in V D between prematurely born and term infants and those prematurely born infants who did or did not develop bronchopulmonary dysplasia (BPD)., Methods: Sixty-one mechanically ventilated infants (15 term, 46 preterm) were studied at a median age of 8 (IQR 2-31) days; 32 of the preterm infants developed BPD. V D was determined from the difference between arterial and end tidal carbon dioxide (CO 2 ) using a low dead space CO 2 detector using the Bohr/Enghoff equation and was related to body weight (V D /kg) at the time of study. The time to peak tidal expiratory flow/expiratory time (T PTEF /T E ) was measured during spontaneous breathing using a fixed orifice pneumotachograph., Results: V D /kg was related to gestational age (r=-0.285, p=0.001), birth weight (r=-0.356, p<0.001), weight (r=-0.316, p<0.001) and postmenstrual age (r=-0.205, p=0.020) at measurement, days of ventilation (r=0.322, p<0.001) and T PTEF /T E (r=-0.397, p=0.003). The median V D /kg was higher in prematurely born infants [2.3 (IQR: 1.7-3.0) ml/kg] compared to term infants [1.5 (1.3-2.1) ml/kg, (p=0.003)] and in premature infants that developed BPD [2.6 (IQR 1.8-3.4) ml/kg] compared to those who did not [1.7 (IQR 1.1-1.9) ml/kg], (p<0.001)., Conclusions: Numerous factors influence pulmonary dead space and thus an optimum tidal volume will differ according to the underlying demographics and respiratory status., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Accurate prediction of extubation outcome could result in a significant reduction of respiratory morbidity in premature neonates., Objectives: To assess whether the respiratory muscle time constant of relaxation (τ) predicted extubation outcome in mechanically ventilated, premature infants., Methods: Forty-six mechanically ventilated infants with a median gestational age of 26 (interquartile range [IQR] 25-29) weeks were prospectively studied. τ was calculated from the reciprocal of the slope of the decline in airway pressure as a function of time. Measurements of τ were done during 5-10 min of a spontaneous breathing test (SBT) prior to extubation. During the first and last minute of the SBT, τ1 and τ2, respectively, were assessed, and the difference between them was calculated (Δτ)., Results: The median τ2 was significantly higher in infants whose extubation failed (20.7 [IQR 12.9-34.7] s/cm H2O) than in infants whose extubation succeeded (8.2 [IQR 6.2-17.8] s/cm H2O, p = 0.002). The median Δτ was significantly higher in infants whose extubation failed (10.3 [IQR 4.4-23.9] s/cm H2O) than in infants whose extubation succeeded (-1.63 [IQR -5.7 to 0.3] s/cm H2O, p = 0.001). Extubation failure was associated with τ2 (p = 0.011) and Δτ (p = 0.010) after correcting for postmenstrual age, patent ductus arteriosus, and intraventricular haemorrhage. Receiver operator characteristic curve analysis demonstrated that Δτ predicted extubation failure with an area under the curve of 0.937. A Δτ of +1.02 s/cm H2O predicted extubation failure with 94% sensitivity and 83% specificity., Conclusions: The respiratory muscle time constant of relaxation during an SBT was significantly greater in infants whose extubation failed and could be used to predict extubation outcome in prematurely born infants., (© 2017 S. Karger AG, Basel.)

We hypothesized that radiographically-assessed hyperinflation in bronchopulmonary dysplasia (BPD) is related to the degree of oxygenation impairment. Our objective was to explore the relation of chest radiographic thoracic area (CRTA) with right-to-left shunt, right shift of the oxyhemoglobin dissociation curve and ventilation/perfusion ratio (VA/Q) in infants with BPD. Twenty-two infants born at median (IQR) gestation of 26 (24-28) weeks with BPD were prospectively studied at 39 (30-69) days. Inspired oxygen (FiO2) was varied to obtain transcutaneous oxygen saturation (SpO2) values between 85 and 96%. Shunt, shift and VA/Q were derived by plotting and analysing pairs of SpO2 and FiO2. CRTA was measured by free hand-tracing the perimeter of the thoracic area in anterio-posterior chest radiographs. Median (IQR) shunt was 8 (1-14)%, shift was 13 (11-19)kPa and VA/Q 0.42 (0.30-0.48). Median (IQR) CRTA/kg was 2495 (1962-2838)mm(2) and was significantly related to shift (r=0.674, p<0.001), VA/Q (r=-0.633, p<0.001), weight at study (r=-0.457, p=0.003) and day of life (r=-0.406, p=0.009), but not to shunt. CRTA in BPD is significantly related to oxygenation impairment as quantified by shift and VA/Q. CRTA can be used as a simple radiographic test to quantify BPD severity., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Patients with cystic fibrosis (CF) are at increased risk of inspiratory muscle fatigue and respiratory failure. The time constant (τ) of the inspiratory muscle relaxation is a simple bedside test of muscle fatigue. We have compared patients with CF and healthy controls regarding τ and hypothesized that it is negatively associated with severity of lower airway obstruction., Methods: For this cross-sectional study, τ after maximal inspiration and spirometric indices (forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)) were measured., Results: Fifty-three CF patients (median age 14 y (interquartile range: 11-19.5)) and 53 age- and sex-matched healthy control subjects (14 y (11-19.5)) were recruited. Application of a general linear model revealed that health status (CF vs. non-CF) had a significant effect on τ (P < 0.001), but age group and the interaction of age group with health status did not have significant effects on τ (P = 0.10 and P = 0.71, respectively). Participants with CF had significantly higher τ (253 (188-406)) than control subjects (117 (81-185)) (P < 0.001) and τ was negatively related to FEV1 (r = -0.205; P = 0.031) and FVC (r = -0.294; P = 0.002)., Conclusion: Patients with CF have higher τ than healthy controls but the correlation of τ with expiratory flow function is modest.

Respiratory failure constitutes the major cause of morbidity and mortality in patients with Cystic Fibrosis (CF). Respiratory failure could either be due to lung parenchyma damage or to insufficiency of the respiratory pump which consists of the respiratory muscles, the rib cage and the neuromuscular transmission pathways. Airway obstruction, hyperinflation and malnutrition have been historically recognised as the major determinants of respiratory pump dysfunction in CF. Recent research has identified chronic infection, genetic predisposition, dietary and pharmaceutical interventions as possible additional determinants of this impairment. Furthermore, new methodological approaches in assessing respiratory pump function have led to a better understanding of the pathogenesis of respiratory pump failure in CF. Finally, respiratory muscle function could be partially preserved in CF patients with structured interventions such as aerobic exercise, inspiratory muscle training and non-invasive ventilation and CF patients could consequently be relatively protected from respiratory fatigue and respiratory failure., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Classifying the severity of bronchopulmonary dysplasia (BPD) by continuous numerical variables would facilitate follow-up of disease progression and quantified analysis of disease determinants., Objectives: To non-invasively measure oxygenation impairment in BPD by the degree of right-to-left shunt, right shift of the oxyhaemoglobin dissociation curve and ventilation/perfusion (VA/Q) inequality and to explore their relation with clinical parameters., Methods: Prospective cohort study of 24 infants with a median (interquartile range, IQR) gestation of 25 weeks (24-27) and a birth weight of 0.70 kg (0.63-0.93), studied at 36 days (30-66), at a postmenstrual age (PMA) of 33 weeks (29-36). Inspired oxygen (FIO2) was varied to obtain three to five transcutaneous oxygen saturation (SpO2) values between 85 and 96%. Values of shunt, shift and VA/Q were obtained by plotting the paired data of SpO2 against FIO2 for each infant using a unique program. Right-to-left shunt, right shift of the oxyhaemoglobin dissociation curve and VA/Q were measured in infants born <32 weeks PMA receiving oxygen at 28 days., Results: The median (IQR) shunt was 8% (0.3-16.5), shift 14.5 kPa (10.9-19.4) and VA/Q 0.40 (0.30-0.48). Shunt, shift and VA/Q were significantly related to gestational age (GA) at birth, PMA at study, weight at study and weight gain per week., Conclusions: Severity of pulmonary oxygenation impairment in BPD can be quantified at the cot-side by non-invasive measurement of shunt, shift and VA/Q. Low GA at birth, low weight at birth and at the time of study and impaired weight gain are significantly associated with the severity of oxygen-exchange impairment in infants with BPD., (© 2015 S. Karger AG, Basel.)

Background: Chronic infection with Pseudomonas aeruginosa in patients with cystic fibrosis (CF) is associated with increased morbidity. Chronic infection can cause limb and respiratory muscle compromise. Respiratory muscle function can be assessed via maximal inspiratory pressure (PImax), maximal expiratory pressure (PEmax), and the pressure-time index of the respiratory muscles (PTImus). We studied the effect of chronic P. aeruginosa infection on respiratory muscle function in patients with CF., Methods: This cross-sectional study assessed PImax, PEmax, PTImus, FEV1, FVC, maximum expiratory flow during the middle half of the FVC maneuver, body mass index, and upper arm muscle area in 122 subjects with CF, in 4 subgroups matched for age and sex at different stages of P. aeruginosa infection, according to the Leeds criteria. We compared respiratory muscle function in the subgroups according to P. aeruginosa infection state., Results: Median PImax was significantly lower in CF subjects with chronic P. aeruginosa infection (PImax = 62 cm H2O), compared to subjects who were never infected (PImax = 86 cm H2O, P = .02), free of infection (PImax = 74 cm H2O, P = .01), or intermittently infected (PImax = 72 cm H2O, P = .02). Median PTImus was significantly increased in CF subjects with chronic P. aeruginosa infection (PTImus = .142), compared to subjects who were free of infection (PTImus = .102, P = .006). Median upper-arm muscle area was significantly lower in CF subjects with chronic P. aeruginosa infection (upper-arm muscle area = 2,219 mm(2)), compared to subjects who were never infected (2,754 mm(2), P = .03), free of infection (2,678 mm(2), P = .01), or intermittently infected (2,603 mm(2), P = .04). Multivariate logistic regression revealed P. aeruginosa state of infection as a significant determinant of PTImus (P = .03) independently of sex, upper-arm muscle area, and FEV1., Conclusions: CF subjects with chronic P. aeruginosa infection exhibited impaired respiratory muscle function and decreased inspiratory muscle strength, and chronic P. aeruginosa infection independently impacts respiratory muscle function in subjects with CF.

Aim: Whole body hypothermia (WBH) exerts proven neuroprotective effects in infants with hypoxic-ischaemic encephalopathy (HIE). Our aim was to describe how WBH could impact on respiratory function in mechanically ventilated newborn infants, by recording primary and composite indices of oxygenation and ventilation before, during and after WBH., Methods: The medical notes of 31 mechanically ventilated full-term newborn infants who underwent WBH for HIE were retrospectively reviewed. Fraction of inspired oxygen (FiO2), tidal volume (TV), mean airway Pressure (MAP), minute ventilation (MV), static compliance of the respiratory system (C(statRS)), ventilation efficiency index (VEI), alveolar-arterial gradient (A-a gradient) and oxygenation index (OI) were documented before and during hypothermic treatment, as well as during and after rewarming., Results: Fraction of inspired oxygen, MAP, OI and A-a gradient decreased during induction of hypothermia and tended to increase during rewarming. C(statRS), VEI and TV increased during induction of hypothermia and tended to decrease during rewarming. None of the changes achieved statistical significance., Conclusion: These results suggest that WBH might affect respiratory function in mechanically ventilated infants with HIE. Oxygenation might be enhanced by hypothermia, probably as a result of decreased metabolism, while ventilation might also be facilitated as a result of the effect of hypothermia on lung mechanics., (©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Milk proteins have attracted extensive interest in terms of their bioavailability following ingestion. Enzymatic digestion of dairy products generates numerous peptides with various biological activities. Both human milk and infant formulas based on cow's milk are potential sources of bioactive peptides. This review aims to present current knowledge on the formation and fate of bioactive peptides from milk feeds intended for infants. Emphasis is placed on the source of the bioactive peptides with the nutritional impact of human milk and cow milk-based formulas on infant health being critically discussed from that perspective. Furthermore, the effect of processing and in vitro or in vivo digestion on the release and availability of peptides with bioactive sequences is evaluated. Considerable differences with respect to bioavailability and metabolic effects between the biologically active fragments generated following ingestion of human milk and infant formulas are documented. Peptides from milk protein of bovine origin could be a valuable supplement to human milk as multiple health-promoting properties are attributed to peptide fractions identified in standard cow milk-based infant formulas.

Respiratory muscle function in patients with cystic fibrosis (CF) can be assessed by measurement of maximal inspiratory pressure (Pimax ), maximal expiratory pressure (Pemax ), and pressure-time index of the respiratory muscles (PTImus ). We investigated the differences in maximal respiratory pressures and PTImus between CF patients with no gross hyperinflation and healthy controls and described the effects of pulmonary function and nutrition impairment on respiratory muscle function in this group of CF patients. Forced expiratory volume in 1 sec (FEV1 ), forced vital capacity (FVC) and maximal expiratory flow between 25% and 75% of VC (MEF25-75 ), body mass index (BMI), upper arm muscle area (UAMA), Pimax , Pemax , and PTImus were assessed in 140 CF patients and in a control group of 140 healthy subjects matched for age and gender. Median Pimax and Pemax were significantly lower in CF patients compared to the controls [Pimax  = 74 (57-94) in CF vs. 84 (66-102) in controls, P = 0.009], [Pemax  = 71 (50-95) in CF vs. 84 (66-102) in controls, P < 0.001]. Median PTImus in CF patients compared to controls was significantly increased [PTImus  = 0.110 (0.076-0.160) in CF vs. 0.094 (0.070-0.137) in controls, P = 0.049] and it was significantly higher in CF patients with impaired pulmonary function. In CF patients, PTImus was significantly negatively related to upper arm muscle area (r = 0.184, P = 0.031). These findings suggest that CF patients with no severe lung disease compared to healthy subjects exhibit impaired respiratory muscle function, while CF patients with impaired pulmonary function and nutrition indices exhibit higher PTImus values., (Copyright © 2012 Wiley Periodicals, Inc.)

A fetus was diagnosed by prenatal ultrasound with bilateral intrauterine pleural effusions that were subsequently drained in utero by insertion of bilateral thoracoamniotic shunts. Serial prenatal ultrasound scans were consistent with a left-sided diaphragmatic hernia. On the first day of life, the infant underwent an exploratory laparotomy for intestinal obstruction, with radiographic findings of pneumatosis intestinalis. Intraoperative findings were suggestive of prenatal bowel and diaphragm perforation, which might have occurred as a complication of thoracoamniotic shunting.

Background: The beneficial role of exercise in maintaining health in patients with cystic fibrosis (CF) is well described. Few data exist on the effect of exercise on respiratory muscle function in patients with CF. Our objective was to compare respiratory muscle function indices in CF patients that regularly exercise with those CF patients that do not., Methods: This cross-sectional study assessed nutrition, pulmonary function and respiratory muscle function in 37 CF patients that undertook regular aerobic exercise and in a control group matched for age and gender which consisted of 44 CF patients that did not undertake regular exercise. Respiratory muscle function in CF was assessed by maximal inspiratory pressure (Pimax), maximal expiratory pressure (Pemax) and pressure-time index of the respiratory muscles (PTImus)., Results: Median Pimax and Pemax were significantly higher in the exercise group compared to the control group (92 vs. 63 cm H2O and 94 vs. 64 cm H2O respectively). PTImus was significantly lower in the exercise group compared to the control group (0.089 vs. 0.121). Upper arm muscle area (UAMA) and mid-arm muscle circumference were significantly increased in the exercise group compared to the control group (2608 vs. 2178 mm2 and 23 vs. 21 cm respectively). UAMA was significantly related to Pimax in the exercising group., Conclusions: These results suggest that CF patients that undertake regular aerobic exercise maintain higher indices of respiratory muscle strength and lower PTImus values, while increased UAMA values in exercising patients highlight the importance of muscular competence in respiratory muscle function in this population., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Respiratory muscle function in patients with cystic fibrosis (CF) has been studied by measurement of maximal inspiratory pressure (P(Imax)), maximal expiratory pressure (P(Emax)), and the pressure-time index of the respiratory muscles (PTI(mus)). The maximum rate of pressure development (MRPD) during P(Imax) (MRPD-P(Imax)), MRPD during P(Emax) (MRPD-P(Emax)), maximal relaxation rate (MRR) during P(Imax) (MRR-P(imax)), and MRR during P(Emax) (MRR-P(Emax)) have not been studied in CF. Our aim was to study MRPD and MRR and investigate their possible application as accessory indices of respiratory muscle function in patients with CF., Methods: FEVY, FVC, and maximal expiratory flow between 25% and 75% of vital capacity, body mass index (BMI), upper arm muscle area, P(imax), P(Emax), PTI(mus), MRPD-P(Imax), MRPD-P(Emax), MRR-P(imax), and MRR-P(Emax) were assessed in 123 CF patients and in a control group of 123 healthy subjects matched for age and sex., Results: MRR-P(Emax) was significantly increased and MRPD-P(Emax) was significantly decreased in the CF patients, compared to the healthy controls. In the CF patients MRR-P(Imax) was significantly related to PTI(mus) (P = .02), FEV1 (P = .03), FVC (P = .001), BMI (P < .001), and upper arm muscle area (P < .001). In the CF patients, MRPD-P(Imax) and MRPD- P(Emax) were significantly related to upper arm muscle area (P < .001), BMI (P < .001 and P = .01, respectively), P(Imax) (P < .001), and P(Emax) (P < .001)., Conclusions: The CF patients exhibited increased MRR and decreased MRPD during maximal respiratory effort, compared to controls. The differences in MRR-P(imax) and MRPD-P(Imax) between the controls and the complete group of CF patients were not significant. MRPD and MRR were significantly related to nutritional and pulmonary function impairment in CF patients. MRPD strongly correlated to maximal respiratory muscle pressures, and MRR strongly correlated to PTI(mus) in patients with CF. These findings suggest that CF patients are at increased risk of respiratory muscle fatigue. Regular determination of MRPD and MRR may be clinically useful in CF patients and help to initiate inspiratory muscle training and noninvasive ventilation.

Background: Tobacco use in pregnancy is considered a human developmental toxicant and potential teratogen. The aim of the study was to test for a possible association between periconceptional tobacco smoking and congenital heart disease (CHD) in the neonatal period., Methods: Maternal and infant characteristics of 157 neonates diagnosed with CHD at the University of Patras Medical School were collected and were compared with 208 normal neonates (aged 1-28 days) that were referred for echocardiography during a specified 3-year period., Results: In neonates with CHD 64 of 157 mothers (40.8%) reported smoking in pregnancy, whereas in the control group 41 of 208 mothers (19.7%) were smokers (p=0.000). Logistic regression analysis with pregestational diabetes, history of influenza-like illness in the first trimester, therapeutic drug exposure in pregnancy, maternal age, parity, family history of CHD, infant gender, prematurity and paternal smoking, as potential confounding factors showed that periconceptional tobacco smoking was associated with increased risk of CHD in the offspring (OR=2.750, 95% CI=1.659-4.476, p=0.00001). The incidence of neonatal heart disease in women who were non-smokers or smoked 1-10 and ≥11 cigarettes per day increased with the level of fetal tobacco exposure (35.8% versus 55.3% versus 64.3%, x2-test=20.303, p=0.000), suggesting a dose effect., Conclusions: The results of the study are indicative of an association between periconceptional tobacco exposure and increased risk of CHD in the neonatal period. The potential role of gestational smoking as a risk factor for specific heart defect subgroups requires the conduction of large population based epidemiological studies., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)