David M. Cooper

Lipid peroxidation as determined by plasma isoprostanes is related to disease severity in mild asthma.

Oxidative stress is believed to play an important role in the pathophysiology of asthma. Recently discovered F2-isoprostanes, of which 8-iso-PGF2α is the most well-known isomer, have emerged as the most reliable marker of in vivo oxidative stress. The aim of this study was to examine 8-iso-PGF2α as a biomarker of oxidative stress in mild asthma in relation to endogenous and dietary antioxidant protection. Total (free and esterified) plasma 8-iso-PGF2α, plasma dietary antioxidants (vitamins E and C,β-carotene, Zn, and Se), and erythrocyte antioxidant enzyme activities (glutathione peroxidase and superoxide dismutase) were measured in 15 mild asthmatics and 15 age-and sex-matched controls. Total plasma 8-iso-PGF2α levels [median (quartile 1-quartile 3)] were significantly increased in the sthmatics [213 pg/mL (122–455) vs. 139 pg/mL (109–174), P=0.042]. The 8-iso-PGF2α levels were found to be associated with clinical asthma severity (P=0.044) and inhaled corticosteroid use (P=0.027) in asthmatics. No differences were observed in the plasma dietary antioxidant vitamins. The asthmatics had significantly lower plasma levels of Zn (P=0.027) and Se (P=0.006). Plasma Se correlated negatively with 8-iso-PGF2α (r=−0.725, P=0.002). No differences between the groups were observed for glutathione peroxidase or superoxide dismutase, however, superoxide dismutase activity was negatively associated with asthma severity (P=0.042). In conclusion, oxidative stress is increased in mild asthmatics, as reflected by increased plasma levels of 8-iso-PGF2α and a deficiency in plasma Zn and Se. The isoprostane 8-iso-PGF2α may provide a useful tool in intervention studies aimed at improving clinical status in asthma.

Sleep-related breathing disorder in Duchenne muscular dystrophy: Disease spectrum in the paediatric population

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease with death usually occurring because of respiratory failure. Signs of early respiratory insufficiency are usually first detectable in sleep.

Respiratory morbidity of hospitalized children with Trisomy 21.

Objective: To review the respiratory morbidity in children with Trisomy 21 admitted to a teaching hospital.

Oxidative Stress in Cystic Fibrosis: Dietary and Metabolic Factors

Objective: To examine oxidative stress in CF by measuring 8-iso-PGF2α and antioxidant defenses, in relation to dietary intake, immune function and clinical status. Methods: We measured total plasma concentrations of 8-iso-PGF2α and dietary antioxidants (vitamin E, vitamin C, β-carotene), erythrocyte antioxidant enzyme activities (glutathione peroxidase and superoxide dismutase), lung function and dietary intake in 21 CF subjects and 21 healthy age- and gender-matched controls. Results: Total plasma 8-iso-PGF2α concentration (median [quartile 1–quartile 3]) was significantly higher in CF subjects compared to controls (214 pg/mL (155–331) vs. 135 pg/mL (101–168), p=0.001). Neutrophil, monocyte and total white cell counts were elevated in the CF group and these correlated with 8-iso-PGF2α concentration. Despite similar dietary intake, lower plasma antioxidant concentrations were observed in the CF group (vitamin E, p < 0.001, vitamin C, p=0.004, β-carotene, p=0.001). 8-iso-PGF2α correlated negatively with plasma vitamin E, C and β-carotene concentrations. Conclusion: Oxidative stress is increased in CF patients, despite normal dietary antioxidant intake. The immune response appears to be a key factor causing oxidative stress. Antioxidant intervention aimed at reducing oxidative stress in CF needs to be assessed.

Motor coordination difficulties and physical fitness of extremely-low-birthweight children

Motor coordination difficulties and poor fitness exist in the extremely low birthweight (ELBW) population. This study investigated the relative impact of motor coordination on the fitness of ELBW children aged 11 to 13 years. One hundred and nine children were recruited to the study: 54 ELBW participants (mean age at assessment 12y 6mo; 31 male, 23 female; mean birthweight 769g, SD 148g; mean gestational age 26.6 weeks, SD 2.1 weeks) and 55 comparison children (mean age at assessment 12y 5mo; 28 males, 27 females; at least 37 weeks’ gestation). All children completed the Movement Assessment Battery for Children (MABC), functional tests of postural stability and strength, growth measures, and tests of respiratory function. Maximal oxygen uptake (VO2max) was calculated from a 20m shuttle run test as a measure of fitness. The ELBW group had greater problems with postural stability (p=0.001) and motor coordination (p=0.001), with 70% rated as having a definite motor problem on the MABC brackets (those who scored less than the 5th centile on the MABC). The ELBW was also less fit than the comparison group (p=0.001), with 45% below the 10th centile for VO2max. There were differences between the groups for growth, strength, and particularly respiratory function. However, respiratory function did not significantly correlate with VO2max in the ELBW group. Motor coordination was the most powerful predictor of VO2max in both the ELBW (p=0.001) and the comparison groups (p=0.001).

Safety of bronchoalveolar lavage in young children with cystic fibrosis

Our aim was to determine the safety of BAL in young children <6 years with CF.

Pulse transit time changes observed with different limb positions

Pulse transit time (PTT) is a non-invasive measure of arterial compliance. It can be used to assess instantaneous blood pressure (BP) changes in continual cardiovascular measurement such as during overnight respiratory sleep studies. In these studies, periodic changes in limb position can occur randomly. However, little is known about their possible effects on PTT monitored on the various limbs. The objective of this study was to evaluate PTT differences on all four limbs during two positional changes (lowering and raising of a limb). Ten healthy adults (seven male) with a mean age of 27.0 years were recruited in this study. The results showed that the limb that underwent a positional change had significant (p < 0.05) local PTT differences when compared to its nominal baseline value, whereas PTT changes in the other remaining limbs were insignificant (p > 0.05). The mean PTT value measured from a vertically-raised limb increased by 42.7 ms, while it decreased by 28.1 ms with a half-lowered limb. The PTT differences observed during positional change can be contributed to by the complex interactions between hydrostatic pressure changes, autonomic and local autoregulation experienced in these limbs. Hence the findings herein suggest that PTT is able to reflect local circulatory responses despite changes in the position of other limbs. This can be useful in prolonged clinical observations where limb movements are expected.

Screening of obstructive and central apnoea/hypopnoea in children using variability: a preliminary study.

AIM Polysomnography (PSG) is the current standard protocol for sleep disordered breathing (SDB) investigation in children. Presently, there are limited reliable screening tests for both central (CE) and obstructive (OE) respiratory events. This study compared three indices, derived from pulse oximetry and electrocardiogram (ECG), with the PSG gold standard. These indices were heart rate (HR) variability, arterial blood oxygen de-saturation (SaO2) and pulse transit time (PTT). METHODS 15 children (12 male) from routine PSG studies were recruited (aged 3-14 years). The characteristics of the three indices were based on known criteria for respiratory events (RPE). Their estimation singly and in combination was evaluated with simultaneous scored PSG recordings. RESULTS 215 RPE and 215 tidal breathing events were analysed. For OE, the obtained sensitivity was HR (0.703), SaO2 (0.047), PTT (0.750), considering all three indices (0) and either of the indices (0.828) while specificity was (0.891), (0.938), (0.922), (0.953) and (0.859) respectively. For CE, the sensitivity was HR (0.715), SaO2 (0.278), PTT (0.662), considering all indices (0.040) and either of the indices (0.868) while specificity was (0.815), (0.954), (0.901), (0.960) and (0.762) accordingly. CONCLUSIONS Preliminary findings herein suggest that the later combination of these non-invasive indices to be a promising screening method of SDB in children.

Motion artefact reduction of the photoplethysmographic signal in pulse transit time measurement

Motion artefact is a common occurrence that contaminates photoplethysmographic (PPG) measurements. To extract timing information from signals during artefact is challenging. PPG signal is very sensitive to artefacts and can be used in applications like, pulse transit time (PTT) as part of the polysomnographic studies. A correlation cancellation or signal processing approach is implemented with the adaptive cancelling filter concept and a triaxial accelerometry. PPG signals obtained from a Masimo (Reference) pulse oximeter is used as reference to compare with the reconstructed PPG signals. Different hands are used for each PPG source, one stationary while the other involves typical movements during sleep. A second Masimo pulse oximeter is used to register intensity of timing errors on commercial PPG signals. 108 PTT measurements are recorded in three different movements with PTT estimates from unprocessed PPG signals showing 35.51±27.42%, Masimo 50.02±29.40% and reconstructed 4.32±3.59% difference against those from the Reference PPG. The triaxial accelerometry can be used to detect the presence of artefact on PPG signals. This is useful in PTT measurements when signal contaminated with artefacts are required for further analysis, especially after and during arousals in sleep. The suggested filtering model can then reconstruct these corrupted PPG signals.

Attractor Structure Discriminates Sleep States: Recurrence Plot Analysis Applied to Infant Breathing Patterns

Breathing patterns are characteristically different between infant active sleep (AS) and quiet sleep (QS), and statistical quantifications of interbreath interval (IBI) data have previously been used to discriminate between infant sleep states. It has also been identified that breathing patterns are governed by a nonlinear controller. This study aims to investigate whether nonlinear quantifications of infant IBI data are characteristically different between AS and QS, and whether they may be used to discriminate between these infant sleep states. Polysomnograms were obtained from 24 healthy infants at six months of age. Periods of AS and QS were identified, and IBI data extracted. Recurrence quantification analysis (RQA) was applied to each period, and recurrence calculated for a fixed radius in the range of 0-8 in steps of 0.02, and embedding dimensions of 4, 6, 8, and 16. When a threshold classifier was trained, the RQA variable recurrence was able to correctly classify 94.3% of periods in a test dataset. It was concluded that RQA of IBI data is able to accurately discriminate between infant sleep states. This is a promising step toward development of a minimal-channel automatic sleep state classification system.