Theodore Dassios

Respiratory muscle function in patients with cystic fibrosis.

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. Pediatr Pulmonol. 2013; 48:865–873.

Periconceptional tobacco smoking and Xisolated congenital heart defects in the neonatal period

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.

Aerobic exercise and respiratory muscle strength in patients with cystic fibrosis

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.

Using Measurements of Shunt and Ventilation-to-Perfusion Ratio to Quantify the Severity of Bronchopulmonary Dysplasia

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.

Time constant of inspiratory muscle relaxation in cystic fibrosis

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.

Correlation of radiographic thoracic area and oxygenation impairment in bronchopulmonary dysplasia

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.

Relaxation Rate of the Respiratory Muscles and Prediction of Extubation Outcome in Prematurely Born Infants

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.

Admissions for hypoglycaemia after 35 weeks of gestation: perinatal predictors of cost of stay

Abstract Background: Hypoglycaemia accounts for approximately one-tenth of term admissions to neonatal units can cause long-term neurodevelopmental impairment and is associated with the significant burden to the affected infants, families and the health system. Objective: To define the prevalence, length and cost of admissions for hypoglycaemia in infants born at greater than 35 weeks gestation and to identify antenatal and perinatal predictors of those outcomes. Materials and methods: This was a retrospective audit of infants admitted for hypoglycaemia between 1 January 2012 and 31 December 2015, in a level three neonatal intensive care unit at King’s College Hospital NHS Foundation Trust, London. The main outcome measures were the prevalence, length and cost of admissions for hypoglycaemia and antenatal and postnatal predictors of the length and cost of the stay. Results: There were 474 admissions for hypoglycaemia (17.8% of total admissions). Their median (IQR) blood glucose on admission was 2.1 (1.7–2.4) mmol/l, gestation at delivery 38.1 (36.7–39.3) weeks, birthweight percentile 31.4 (5.4–68.9), their length of stay was 3.0 (2.0–5.0). Admissions equated to a total of 2107 hospital days. The total cost of the stay was 1,316,591 Great Britain pound. The antenatal factors associated with admission for hypoglycaemia were maternal hypertension (19.8%), maternal diabetes (24.5%), foetal growth restriction (FGR) (25.9%) and pathological intrapartum cardiotocograph (23.4%). In 13.7% of cases, there was no associated pregnancy complication. Multivariate logistic regression analysis demonstrated lower gestational age, z-score birthweight squared, exclusive breastfeeding and maternal prescribed nifedipine were independently associated with the length and cost of the stay. Conclusion: Hypoglycaemia accounted for approximately one-fifth of admissions after 35-week gestation. Lower gestational age and admission blood glucose, low and high z-score birthweight, maternal nifedipine and exclusive breastfeeding are associated with longer duration of stay.

Functional morphometry for the estimation of the alveolar surface area in prematurely-born infants

Conventionally, the alveolar surface area (SA) has been measured by using post-mortem morphometry. Such studies have highlighted that SA in prematurely-born infants is markedly smaller when compared to term-born infants as a result of postnatal impairment or arrest of alveolar development. We herein explore how, non-invasive measurements of the ventilation/perfusion ratio (VA/Q) can be used to estimate SA in prematurely-born surviving, convalescent infants. We also compare SA in prematurely-born infants measured at term-corrected age, to term-born infants using previously published datasets of VA/Q. Ficks first law of diffusion is employed for the conversion of VA/Q measurements to SA values after correcting for differences in pulmonary perfusion, thickness of the respiratory membrane and alveolar-arterial gradient. We report that SA is fivefold smaller in prematurely-born compared to term-born infants. We conclude that non-invasive measurements of VA/Q can be used for the functional estimation of SA which could, in turn, be used as a future outcome measure in respiratory studies of prematurely-born infants.

Nutritional status and pulmonary outcome in children and young people with cystic fibrosis

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 (r2 = 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.